1. bookTom 16 (2022): Zeszyt 1 (February 2022)
Informacje o czasopiśmie
License
Format
Czasopismo
eISSN
1875-855X
Pierwsze wydanie
01 Jun 2007
Częstotliwość wydawania
6 razy w roku
Języki
Angielski
access type Otwarty dostęp

PIWI-interacting RNA (piRNA): a narrative review of its biogenesis, function, and emerging role in lung cancer

Data publikacji: 28 Feb 2022
Tom & Zeszyt: Tom 16 (2022) - Zeszyt 1 (February 2022)
Zakres stron: 3 - 14
Informacje o czasopiśmie
License
Format
Czasopismo
eISSN
1875-855X
Pierwsze wydanie
01 Jun 2007
Częstotliwość wydawania
6 razy w roku
Języki
Angielski
Abstract

Cancer remains elusive in many aspects, especially in its causes and control. After protein profiling, genetic screening, and mutation studies, scientists now have turned their attention to epigenetic modulation. This new arena has brought to light the world of noncoding RNA (ncRNA). Although very complicated and often confusing, ncRNA domains are now among the most attractive molecular markers for epigenetic control of cancer. Long ncRNA and microRNA (miRNA) have been studied best among the noncoding genome and huge data have accumulated regarding their inhibitory and promoting effects in cancer. Another sector of ncRNAs is the world of PIWI-interacting RNAs (piRNAs). Initially discovered with the asymmetric division of germline stem cells in the Drosophila ovary, piRNAs have a unique capability to associate with mammalian proteins analogous to P-element induced wimpy testis (PIWI) in Drosophila and are capable of silencing transposons. After a brief introduction to its discovery timelines, the present narrative review covers the biogenesis, function, and role of piRNAs in lung cancer. The effects on lung cancer are highlighted under sections of cell proliferation, stemness maintenance, metastasis, and overall survival, and the review concludes with a discussion of recent discoveries of another class of small ncRNAs, the piRNA-like RNAs (piR-Ls).

Keywords

Lung cancer causes the highest mortality in cancer-related deaths worldwide [1]. One of the major causes of lung cancer is tobacco smoking, which may be associated with socioeconomic status [2, 3]. While raising awareness is necessary to control the growing incidence of lung cancer, understanding the cellular networks and discovering new targets for therapies are also important. In recent trends, scientists have examined the pool of noncoding RNAs (ncRNAs) and their specific roles in epigenetic regulation. So far, the most studied ncRNAs are microRNAs (miRNAs) and their regulatory roles in various cancers, including lung cancer, have been established [4].

P-element induced wimpy testis (PIWI) proteins belong to the Argonaute family of proteins [5], which were first discovered in Drosophila melanogaster ovarian germ cells and follicular cells [6]. By interacting with Tudor domain-containing proteins (TDRDs), PIWI proteins mediate the biogenesis of PIWI-interacting RNAs (piRNAs), thereby silencing transposons [7]. Three types of PIWI subfamily proteins are found in Drosophila—piwi, which localizes in the nucleus of germ and gonadal somatic cells, Aubergine (aub), and Archipelago 3 or Argonaute 3 (ago3), which are both expressed in nuages, or germline granules, which are special cytoplasmic compartments in Drosophila melanogaster. All these proteins are involved in the biogenesis of piRNAs in Drosophila flies [8]. PIWI proteins use piRNAs as their guide to the specific DNA sequences for transposon silencing and gene regulation as well as playing major roles in their biogenesis [9]. Orthologs of Drosophila piwi proteins have been found in mice, zebrafish, C. elegans, and humans, in which they have similar roles in maintaining male and female fertility (Figure 1). In the human, genome 4 piwi orthologs (PIWIL1/HIWI, PIWIL2/HILI, PIWIL3, and PIWIL4/HIWI2) have been identified [5]. The first evidence of human PIWI association with cancer was studied in seminomas [14]. Aberrant expression of 1 or more of these 4 proteins is common, especially in breast, prostate, and colorectal carcinomas (Table 1). Limited findings have emerged in the case of lung cancer [4, 60,61,62]. Various studies have found interesting patterns of human PIWI-like protein expression and regulatory effects in lung cancers [63]. Human PIWIs and piRNAs may be important biomarkers and therapeutic targets for various cancers [64, 65].

Figure 1

Early discoveries related to PIWI proteins and piRNA. piRNA, PIWI-interacting RNA; PIWI, P-element induced wimpy testis protein.

Important discoveries of PIWI/piRNA expression in various cancers

Year PIWI/piRNA Expression Cancer type Role
2005 PIWIL2 Upregulated Testicular seminoma Inhibition of apoptosis and promotion of proliferation via Stat3/Bcl-XL signaling pathway [18]
2006 PIWIL1 Upregulated Human gastric cancer Cell proliferation [19]
2007 PIWIL1 Upregulated Soft tissue sarcoma Stem cell proliferation [20]
2008 PIWIL1 Up/down-regulated Adenocarcinoma Poor prognosis and death [21]
2009 PIWIL1 Presence in cytoplasm Esophageal squamous cell carcinoma Poor prognosis [22]
2010 PIWIL2 Varied Cervical neoplasia Biomarker [23]
2010 PIWIL2 Upregulated Human breast cancers Biomarker [24]
2011 PIWIL1 Upregulated Glioma Tumor progression, poor outcome, and biomarker [25]
2011 piR-651 Upregulated Gastric, colon, lung, and breast cancer Increases cell proliferation [26]
2011 PIWIL1 Upregulated Colorectal cancer Leads to poor overall survival, biomarker [27]
2012 piR-823 Downregulated Gastric cancer Increases cell proliferation [28]
2012 PIWIL2 Upregulated Colon cancer Metastasis [29]
2013 PIWI Upregulated Stage III epithelial ovarian cancer Promotes metastasis, biomarker [30]
2013 piR-932 Upregulated Breast cancer Positive regulator of breast cancer stem cells [31]
2014 PIWIL1 Upregulated Human breast cancer Cell proliferation [32]
2014 piRNA-823 Upregulated Multiple myeloma Regulates angiogenesis [33]
2014 PIWIL1 and PIWIL4 Varied Renal cell carcinoma Related to clinicopathological parameters [34]
2014 PIWIL1 Upregulated Cervical cancer Promotes chemoresistance [35]
2014 PIWIL1 Upregulated Hepatocellular carcinoma Reduces proliferation and migration [36]
2015 piRNA-DQ594040 Downregulated Bladder cancer Promotes cell proliferation, colony formation and functions against apoptosis [37]
2015 piR-021285 Upregulated Breast cancer Epigenetic remodeling [38]
2015 PIWIL2 Upregulated Prostate cancer Metastasis [39]
2015 piR-017061 Downregulated Pancreatic cancer Associated with diseased condition [40]
2015 piR-015551 Downregulated Colorectal cancer Associated with long ncRNA expression [41]
2015 PIWIL1 Downregulated Chronic myeloid leukemia Induces growth and metastasis [42]
2015 PIWIL2 Upregulated Cholangiocarcinoma Involved in shorter survival span and metastasis [43]
2015 piR-57125 Downregulated Renal cell carcinoma Associated with tumor recurrence and metastasis, prognostic biomarker [44]
piR-30924 Upregulated
piR-38756 Upregulated
2015 PIWIL1 Upregulated Type 1 endometrial cancer Tumor progression by downregulating PTEN [45]
2015 PIWIL2 Downregulated Bladder cancer Related to disease specific and progression free survival [46]
2016 PIWIL4 Upregulated Breast cancer Metastasis, antiapoptotic activity and proliferation[47]
2016 FR140858 Differentially expressed Head and neck squamous cell carcinoma Correlated to human papillomavirus infection [48]
2016 piR-598 Upregulated Glioma Induces growth and proliferation [49]
2017 PIWIL3 Upregulated Melanoma Induces metastasis [50]
2017 PIWIL4 Upregulated Retinoblastoma Induces proliferation [51]
2018 piR-5937 Varied Colon cancer Biomarker [52]
piR-28876
2018 piR-8041 Downregulated Glioblastoma Related to tumor growth [53]
2018 PIWIL1 Upregulated Gastric cancer Metastasis [54]
2018 PIWIL1 and PIWIL2 Varied Muscle invasive urothelial bladder cancer Correlation with clinical factors, biomarkers [55]
2018 PIWIL4 Upregulated Human breast cancer Cell motility [56]
2019 piR-823 Upregulated Multiple myeloma Tumor progression [57]
2019 piR-39980 Upregulated Neuroblastoma Tumor progression and drug resistance [58]
2019 piR-36712 Downregulated Breast cancer Chemoresistance and tumor progression [59]
2020 piR-004987 Upregulated Lung cancer Correlated with lung cancer from sputum as compared with normal [60]
piR-020809 Upregulated
piR-023338 Downregulated
piR-011186 Downregulated
2021 piR-hsa-211106 Downregulated Lung cancer Chemoresistance and tumor progression [61]
2021 piR-1008 Upregulated Lung cancer
piR-28231 Upregulated Lung cancer
piR-11256 Upregulated Lung cancer
piR-30636 Upregulated Lung cancer
piR-24143 Upregulated Lung cancer Biomarker lung cancer [62]
piR-6842 Upregulated Lung cancer
piR-8757 Upregulated Lung cancer
piR-15572 Upregulated Lung cancer
piR-5444 Upregulated Lung cancer and serum exosome
piR-26925 Upregulated

Lung cancer until 2021 and other cancers until 2019. PIWI, PIWI protein (human); piRNA, Piwi protein-interacting RNA; PIWIL1, PIWI-like 1 protein (human) or HIWI protein (human); PIWIL2, HILI protein (human); PIWIL3, HIWI3 protein (human); and PIWIL4, HIWI2 protein (human); ncRNA, non-coding RNA.

The present narrative review aims to introduce the details of piRNA biogenesis and function and then detail the various discoveries as a timeline of events. The review aims to summarize the emerging roles of a relatively new group of sncRNAs, piRNAs, and their interacting PIWI family proteins in lung cancer. Finally, a correlation between the hallmarks of cancer and the piRNA/PIWI family of proteins has been attempted.

Search methodology

We used PubMed (MEDLINE inclusive), Google Scholar, Web of Science, and Scopus as principal online databases. To explore the literature related to PIWI RNA, the keyword “PIWI RNA” was used. To elaborate on its role in cancer the keywords “PIWI RNA” and “cancer” were used. Keywords “PIWI RNA” and “lung cancer” were used to narrow the specification to lung neoplasms. The genesis and logic for separation of dates to demark “PIWI RNA” and “cancer” and “PIWI RNA” and “lung cancer” as detailed in Table 1 was lung cancer until end 2021 and other cancers until 2019. This delimited the information and references related to PIWI RNA and cancers other than lung cancer to 2019. Preference was given to citation of references published in the past 5 years. The reference lists of identified articles were further examined for relevant publications. We have arranged our gathered information using the subtitles indicated in the review and further cross-verified each subheading content with appropriate keywords. We have assembled information for readers for ready reference and have added our personal comments summarizing information acquired along with an attempt to collate piRNA with the basics of cancer biology.

Biogenesis of piRNA

The pathway for piRNA generation is rather complicated and largely uncharted. However, studies conducted so far have confirmed 2 distinct pathways operate in the case of germline and gonadal somatic cells of Drosophila. Precursors of piRNAs are mainly transcribed from gene clusters flamenco and traffic jam. Flamenco is one of the major clusters for piRNA biogenesis in the somatic support cells of the Drosophila ovary and produces piRNA precursors. The cluster resides in the perichromatin region of the X chromosome in Drosophila. An approximately 180 kb stretch of the cluster transcribes into nascent piRNAs, which typically span about 150 kb. The transcripts are generated from a single strand of the DNA by unidirectional transcription orientation in the antisense direction. Partial or an entire loss of flamenco in Drosophila leads to malfunctioning in transposable element (TE) management [66, 67]. A similar, piRNA-producing locus in chromosome 2 in Drosophila is called traffic jam, whose primary function was identified as a crucial factor in gonadal morphogenesis in these flies. Loss of traffic jam leads to blockade in the differentiation of somatic cells into germ cells and ultimately the formation of follicular cells in Drosophila ovaries [68]. Although these 2 clusters are the widely studied and important sources of piRNA, other sources such as intergenic regions and transposons are also noted [69]. In these piRNA regions in the DNA, trimethylated lysine 9 of histone 3 (H3K9Me3) marks are abundant and contribute to piRNA expression [70]. In germ cells, piRNA clusters, to be transcribed, require a protein complex consisting of Rhino, Deadlock, and Cutoff (RDC) proteins [71]. TREX is another complex needed for the dual stranded cluster transcription recruited to the DNA in RDC dependent manner [8]. The length of mature piRNAs varies from 24 to 32 nucleotides [5].

Zucchini mediated pathway

In the gonadal somatic cells and follicular cells, after transcription, the precursors of piRNAs are transported from the nucleus to the Yb body (containing Piwi, Armitage (Armi), Tudor, Vreteno (Vret), RNA helicase Sister of Yb (SoYb)) in the cytosol [72]. Then premature piRNAs are processed at the 5′ end by a mitochondrial membrane endonuclease called Zucchini (Zuc) [73]. Subsequently, they are loaded onto Piwi by Shutdown and Hsp83 and their 3′ end is trimmed by a slicer enzyme [74]. Piwi has a bias for 5′ U. Aub and Ago3 proteins are not used in this pathway. This processed piRNA is further trimmed by a protein called Nibbler [75]. Ultimately, it is methylated at the 2′ O position by a methyltransferase Hen1 (HENMT1 in mice) [76]. This last step is believed to increase the stability of the piRNA. Processed and mature piRNAs are then transferred back to the nucleus.

Ping-pong pathway

The secondary amplification of piRNAs occurs in germ cells with the help of AUB and AGO3 proteins via the ping-pong pathway, which also leads to post-transcriptional gene silencing (PTGS). The ping-pong pathway starts with the loading of nascent piRNAs, transcribed from the clusters to Aub. Aub shows a 5′U bias for piRNAs and Ago3 shows a bias for adenine at the 10th position. The 5′ end is loaded on Aub with the help of the Shu and Hsp83 and then trimmed and methylated as described above for the Zuc mediated pathway [74]. piRNAs loaded onto Aub are antisense to specific TE mRNA and they eventually guide Aub to their complementary TE mRNA in the cytosol for targeted destruction. This process also generates the 5′ piRNA precursor. The primary piRNA precursor is loaded onto Ago3 and processed into secondary piRNA precursors. The secondary piRNA precursor is sense to TE and antisense to unprocessed piRNA; accordingly they cleave the newly attached piRNA precursors and continue the loop of transposon silencing and mature piRNA production [77].

Function
Transposon silencing

piRNAs save the germ cells from mutations by TE. The mechanism of piRNA biogenesis in Drosophila and many other species is itself a process of degrading TE at the post-transcriptional level. Mutations in Aub and Ago3 lead to an elevated level of transposons in the germ cells [78]. As discussed earlier for the ping-pong pathway, a piRNA targets a transposon with opposite orientation and degrades it into a new piRNA. Together these processes serve to slice TE and amplify piRNA. The transposon-containing regions of the DNA generate piRNAs, which in turn upon maturation, recruit Piwi and other proteins to silence the TE region [79, 80]. Other species, such as mice and zebrafish, also show a similar function for their PIWI family proteins. Knocking down of Piwi orthologs increased the abundance of transposons in these species [81].

piRNA mediated epigenetic regulation and transcriptional silencing

Piwi and Aub conduct position effect variegation in which a stretch of euchromatin is converted to heterochromatin to variable extents among cells within the same tissue [82]. Piwi interacts with heterochromatin protein 1a (HP1a) to promote heterochromatin formation [83]. It is shown by studies in Drosophila that Piwi helps in loading the H3K9Me3 mark on DNA and converts stretches of DNA into heterochromatin. So, the loss of Piwi makes TE available for pol II [84]. In mice, Mili and Miwi2 (mouse orthologs of PIWI) together promote retrotransposon silencing by CpG DNA methylation in male germ-line cells and piRNA alone can also regulate DNA methylation in these germ cells [81, 85].

Reproduction and development

PIWI proteins have stem cell maintaining properties for which their role in germline development and maintenance is well observed. Knockdown studies have shown anomalies in development. For instance, in Drosophila both male and female piwi protein-coding gene mutants fail to form primordial germ cells and renew germline stem cells, which leads to sterility [67]. Aub protein-coding gene mutation leads to compromised PTGS and DNA damage accumulation also resulting in sterility [86]. Females with mutant ago3 lay fewer eggs and most of the time are sterile [87]. Similar results were also obtained from studies on mice. PIWI orthologs, Mili, Miwi2, and Miwi mutant mice show defects in PTGS and spermatogenesis [88]. Zebrafish PIWI-like proteins Zili and Ziwi mutations decrease the number of germ cells and increase apoptosis of germ cells respectively [89]. Mutations in other piRNA biogenesis proteins such as Tudor, Vret, and Tej also result in DNA damage and defects in development [74, 79]. piRNA clusters from the chromosomes of Drosophila germ cells play a crucial role in maintaining the integrity of the telomeric regions. Loss of piRNAs in germ cells results in decreased levels of HP1a, Rhino and H3K9Me3 association with the telomeric region and disputed nuclear positioning of the telomere [90]. In silkworms and other insects, PIWI has a role in sex determination. Loss of Bmsiwi (insect PIWI) and histone methyltransferase BmAsh2 causes female-to-male sexual reversal [91].

Translational regulation by PIWI–piRNA pathway

piRNAs can be formed from the 3′UTR region of many protein-coding genes such as vas, traffic jam, and nanos and control the mRNA turnover and protein level expression of these genes. Drosophila flies with piwi mutant flies produce an excess of these gene products, which accumulate in the cell eventually damaging the DNA [70, 92, 93]. Mouse PIWIs interact with eIF4e, which forms a cluster of proteins to control translation [94].

Somatic functions

Although very little evidence has been found so far, studies are suggesting a greater somatic function of the PIWI/piRNA pathway. In the early stages of embryogenesis, Drosophila piwi is needed for chromatin structure maintenance and cell cycle progression [95]. piwi is also found on chromosomes of the salivary gland that mediate epigenetic regulation [96]. Loss of piwi proteins in Drosophila intestinal stem cells impairs the gut regenerative capacity of these flies [97]. In Aplysia, piRNA-mediated DNA methylation is needed for neuronal plasticity [98]. In various arthropods, the PIWI-piRNA pathway may perform as an antiviral defense mechanism in mosquitoes and silkworms [99]. In a rat model of diabetes, activities of pancreatic β-cells may be regulated by piRNAs. β-Cells express thousands of piRNAs and their expression changed when rat Piwi proteins were downregulated, resulting in defective insulin secretion [100]. Besides all these major and minor functions of the PIWI–piRNA pathway in various animals, aberrant expression in human cancers has been reported (Table 1), which will be discussed in detail in the following sections.

Role of PIWI–piRNA in lung cancer
Cell proliferation

Induced expression of PIWIL2 in A549 cells results in increased cell proliferation by elevated expression of CDK2 and cyclin A, both in vitro and in vivo. Similar results are obtained from H460 cells in vitro. By contrast, RNAi-mediated depletion of the protein results in cell cycle arrest (G2/M) and increased apoptosis [101]. An increase in PIWIL1 activity induces cell proliferation in A549 cells and decreases in H1299 cell proliferation when knocked down and increases the colony-forming capacity of tumor cells [63, 102].

A positive correlation of cell proliferation with aberrant expression of piRNAs can be postulated. piR-651 is one example of such piRNAs whose expression is altered significantly in many cancers including in lung cancer patient samples and cancer cell lines such as NCIH446 and 95-D [103]. piR-651 maintains the cell population by keeping proapoptotic proteins in check [103]. Inhibition of piR-651 decreases cell proliferation and increases apoptosis in A549 and HCC827 cells. piR-651 negatively regulates proapoptotic proteins while increasing the activities of antiapoptotic proteins [104]. piR-651 helps cyclin D1 and CDK-4 overexpression and upregulates proliferation of transfected A549 cells both in vitro and in vivo [105]. The expression of RASSF1C has been shown to regulate certain piRNA expression and cancer progression. Upregulation of this oncoprotein correlated with overexpression of piR-52200 and underexpression of piR-35127 inpatient samples while piR-34871 and piR-46545 were additionally up- and downregulated respectively in the non-small-cell lung cancer (NSCLC) cell line H1299 along with the previous 2 piRNAs. In vitro, overexpressing underexpressed and knocking down overexpressed piRNAs decreases cell proliferation. Specifically, knock down of piR-52200 in A549 cells, piR-34871 in HT520 cells decreases cell proliferation significantly. By contrast, H1299 responded in most knockdown and overexpression studies. A low level of colony formation was observed in normal lung tissues after manipulation of piRNA expression [106]. piR-55490 acted as an anticancer agent in vitro and in xenograft studies. In lung cancer cell lines such as A549, H460, and H1299, piR-55490 expression was originally suppressed and upon overexpression, these cell lines showed decreased proliferation. It is postulated that piR-55490 binds to mTOR and degrades it decreasing tumor cell proliferation [107]. Two piRNAs overlapping in the 15th chromosome and sharing a common single nucleotide polymorphism, rs11639347, piR-5247, and piR-5671, increase proliferation of A549 cells [108].

Stemness maintenance

Human PIWI proteins are now proven to maintain the stemness of certain cell populations when present in testis. Hiwi inhibition resulted in the loss of ALDH-1 (cancer cell marker) positive cells and decreased tumor mass in immunocompromised mice when injecting SSClo Aldebr stem cells isolated from an SPC-A1 cell line [109]. Overexpression of RASSF1C promotes CD133+ (stem cell marker) A549 cell tumor sphere formation. RASSF1C induces PIWIL1 expression, which maintains stem cell properties and regulates the wnt/β-catenin pathway. Coexpression of RASSF1C and IGFBP-5 reduces PIWIL1 expression [110].

Metastasis

The interplay between PIWIs and piRNAs aids more than one hallmark of cancer. Inhibition of piR-651 decreases migration of highly invasive cell lines 95-D, A549, and HCC827 cells [106, 107]. Inhibition of PIWIL1 interferes with metastatic activity in H1299 cells, while increased expression induces A549 cell migration [102].

Overall survival

Human case study databases like The Cancer Genome Atlas (TCGA) show a positive correlation between PIWIL1 expression and poor overall survival of patients [102]. Patient samples show similar results, increased PIWIL1 correlating to shorter time to relapse (TTR) and shorter overall survival. Whereas, decreased PIWIL4 correlated with shorter TTR and less overall survival [102]. Patients with higher piR-55490 expression have longer overall survival [107].

piRNA-like short noncoding RNA

Studies in NSCLC and lung squamous cell carcinoma (LSCC) have revealed another class of sncRNAs, the piRNA-Like RNAs (piR-Ls). These RNAs have similar as well as distinguishing features to piRNAs. Two variants have been discovered to date, piR-L-138 and piR-L-163, and both are similar to piRNAs in length. However, 2 major differences are that, unlike piRNAs, they are expressed in adult tissues, and they bind directly to phosphorylated protein targets (p-proteins) to regulate their functional efficacy. Therefore, they are designated as protein functional effector sncRNAs (pfeRNAs). piR-L-138 expression in LSCC increases after cisplatin-based chemotherapy, which eventually leads to chemoresistance by the tumor cells. By contrast, targeting piR-L-138 in LSCC cell lines such as H157 and SKMES-1 increases apoptosis. piR-L-138 regulates p60MDM2 to control cell proliferation [111, 58]. Another study showed piR-L-163 binds to Ezrin, Radixin, and Moesin (p-ERM), which in turn increases the binding capacity of p-ERM to EBP50 and F acting. Blocking piR-L-163 induces cell growth and invasion revealing it as a negative regulator of tumor progression [112].

piRNA biomarker and chemoresistance

Cancer prognosis is related to 2 important facets namely early detection and delayed chemoresistance. In a study with 20 pairs of malignant and nonmalignant tissues, piR-hsa-211106 was downregulated in all malignant tissues as it prevented metastasis and induced apoptosis in lung cancer cells [61]. This piRNA interacts with pyruvate carboxylase, which prevents cisplatin resistivity in lung cancer cells [61].

Lin et al. [60] and Li et al. [62] demonstrated that piRNAs can also be used for diagnosis of lung cancer. Sputum from 32 lung cancer patients was used as a source of epithelial cells from the bronchus and cRNA was profiled [60]. Lung cancer patients had upregulated piR-004987 and piR-020809 expression and downregulated expression of piR-023338 and piR-011186 [60]. Li et al. [62] examined 19 lung tissues from lung cancer patients and compared their piRNA profile with noncancerous lung tissues (from different sites in the same patients). They found 10 piRNAs unregulated in cancerous tissues compared with noncancerous tissue samples (see Table 1). Of these, 2 exosomal piRNAs, namely piR-hsa-26925 and piR-hsa-5444, were found in patient sera. Exosomes are double-layered lipid extracellular vesicles containing macromolecules like nucleic acids (in this case piRNA) used for cell-to-cell communication. Thus, such exosomes identifiable from sera can act as diagnostic markers for lung cancer.

Conclusion

Accumulated data supports the importance of piRNAs in lung and other cancers. Presently we have emphasized lung cancer as it still reigns among all types of cancers in terms of the highest mortality in cancer-related deaths worldwide [1]. Lung cancer management, like any other cancer, revolves around both diagnoses and treatment. For both these factors, detailed molecular understanding of the disease is necessary for an effective outcome. piRNA contributes to cardinal features of cancer development, namely, cell proliferation, stemness maintenance, and metastasis; thus, also reflecting overall survival. Better understanding and clinical interpretation of these noncoding RNAs will not only aid in the understanding of the molecular perturbations, but may also provide insight into the selection of treatment modalities. More detailed screening and identification of anomalous expression of piRNAs may not only help in diagnosis, but also predict the prognosis of the disease. To collate the basics of cancer biology with the advances with knowledge of PIWI proteins or piRNAs, we merged our gathered information with the “Emerging hallmarks and enabling characteristics” as delineated by Hanahan and Weinberg [113, 105]. A diagrammatic representation of how the present finding of PIWI proteins or piRNA integrates with the hallmarks of cancer is depicted in Figure 2. Those PIWI proteins or piRNA that are positively regulated with the hallmarks may serve as a target for lung cancer therapy or as diagnostic or prognostic markers. By contrast, negatively regulated PIWI proteins or piRNA may serve as therapeutic options.

Figure 2

Representation of how the present findings for PIWI proteins or piRNA integrate with the emerging hallmarks of cancer in the case of lung cancer. Turquoise represents positively regulated with the hallmark, while red represents negatively regulated with the hallmark. piRNA, PIWI-interacting RNA; P-element induced wimpy testis protein.

Figure 1

Early discoveries related to PIWI proteins and piRNA. piRNA, PIWI-interacting RNA; PIWI, P-element induced wimpy testis protein.
Early discoveries related to PIWI proteins and piRNA. piRNA, PIWI-interacting RNA; PIWI, P-element induced wimpy testis protein.

Figure 2

Representation of how the present findings for PIWI proteins or piRNA integrate with the emerging hallmarks of cancer in the case of lung cancer. Turquoise represents positively regulated with the hallmark, while red represents negatively regulated with the hallmark. piRNA, PIWI-interacting RNA; P-element induced wimpy testis protein.
Representation of how the present findings for PIWI proteins or piRNA integrate with the emerging hallmarks of cancer in the case of lung cancer. Turquoise represents positively regulated with the hallmark, while red represents negatively regulated with the hallmark. piRNA, PIWI-interacting RNA; P-element induced wimpy testis protein.

Important discoveries of PIWI/piRNA expression in various cancers†

Year PIWI/piRNA Expression Cancer type Role
2005 PIWIL2 Upregulated Testicular seminoma Inhibition of apoptosis and promotion of proliferation via Stat3/Bcl-XL signaling pathway [18]
2006 PIWIL1 Upregulated Human gastric cancer Cell proliferation [19]
2007 PIWIL1 Upregulated Soft tissue sarcoma Stem cell proliferation [20]
2008 PIWIL1 Up/down-regulated Adenocarcinoma Poor prognosis and death [21]
2009 PIWIL1 Presence in cytoplasm Esophageal squamous cell carcinoma Poor prognosis [22]
2010 PIWIL2 Varied Cervical neoplasia Biomarker [23]
2010 PIWIL2 Upregulated Human breast cancers Biomarker [24]
2011 PIWIL1 Upregulated Glioma Tumor progression, poor outcome, and biomarker [25]
2011 piR-651 Upregulated Gastric, colon, lung, and breast cancer Increases cell proliferation [26]
2011 PIWIL1 Upregulated Colorectal cancer Leads to poor overall survival, biomarker [27]
2012 piR-823 Downregulated Gastric cancer Increases cell proliferation [28]
2012 PIWIL2 Upregulated Colon cancer Metastasis [29]
2013 PIWI Upregulated Stage III epithelial ovarian cancer Promotes metastasis, biomarker [30]
2013 piR-932 Upregulated Breast cancer Positive regulator of breast cancer stem cells [31]
2014 PIWIL1 Upregulated Human breast cancer Cell proliferation [32]
2014 piRNA-823 Upregulated Multiple myeloma Regulates angiogenesis [33]
2014 PIWIL1 and PIWIL4 Varied Renal cell carcinoma Related to clinicopathological parameters [34]
2014 PIWIL1 Upregulated Cervical cancer Promotes chemoresistance [35]
2014 PIWIL1 Upregulated Hepatocellular carcinoma Reduces proliferation and migration [36]
2015 piRNA-DQ594040 Downregulated Bladder cancer Promotes cell proliferation, colony formation and functions against apoptosis [37]
2015 piR-021285 Upregulated Breast cancer Epigenetic remodeling [38]
2015 PIWIL2 Upregulated Prostate cancer Metastasis [39]
2015 piR-017061 Downregulated Pancreatic cancer Associated with diseased condition [40]
2015 piR-015551 Downregulated Colorectal cancer Associated with long ncRNA expression [41]
2015 PIWIL1 Downregulated Chronic myeloid leukemia Induces growth and metastasis [42]
2015 PIWIL2 Upregulated Cholangiocarcinoma Involved in shorter survival span and metastasis [43]
2015 piR-57125 Downregulated Renal cell carcinoma Associated with tumor recurrence and metastasis, prognostic biomarker [44]
piR-30924 Upregulated
piR-38756 Upregulated
2015 PIWIL1 Upregulated Type 1 endometrial cancer Tumor progression by downregulating PTEN [45]
2015 PIWIL2 Downregulated Bladder cancer Related to disease specific and progression free survival [46]
2016 PIWIL4 Upregulated Breast cancer Metastasis, antiapoptotic activity and proliferation[47]
2016 FR140858 Differentially expressed Head and neck squamous cell carcinoma Correlated to human papillomavirus infection [48]
2016 piR-598 Upregulated Glioma Induces growth and proliferation [49]
2017 PIWIL3 Upregulated Melanoma Induces metastasis [50]
2017 PIWIL4 Upregulated Retinoblastoma Induces proliferation [51]
2018 piR-5937 Varied Colon cancer Biomarker [52]
piR-28876
2018 piR-8041 Downregulated Glioblastoma Related to tumor growth [53]
2018 PIWIL1 Upregulated Gastric cancer Metastasis [54]
2018 PIWIL1 and PIWIL2 Varied Muscle invasive urothelial bladder cancer Correlation with clinical factors, biomarkers [55]
2018 PIWIL4 Upregulated Human breast cancer Cell motility [56]
2019 piR-823 Upregulated Multiple myeloma Tumor progression [57]
2019 piR-39980 Upregulated Neuroblastoma Tumor progression and drug resistance [58]
2019 piR-36712 Downregulated Breast cancer Chemoresistance and tumor progression [59]
2020 piR-004987 Upregulated Lung cancer Correlated with lung cancer from sputum as compared with normal [60]
piR-020809 Upregulated
piR-023338 Downregulated
piR-011186 Downregulated
2021 piR-hsa-211106 Downregulated Lung cancer Chemoresistance and tumor progression [61]
2021 piR-1008 Upregulated Lung cancer
piR-28231 Upregulated Lung cancer
piR-11256 Upregulated Lung cancer
piR-30636 Upregulated Lung cancer
piR-24143 Upregulated Lung cancer Biomarker lung cancer [62]
piR-6842 Upregulated Lung cancer
piR-8757 Upregulated Lung cancer
piR-15572 Upregulated Lung cancer
piR-5444 Upregulated Lung cancer and serum exosome
piR-26925 Upregulated

Cai Z, Liu Q. Understanding the Global Cancer Statistics 2018: implications for cancer control. Sci China Life Sci. 2021; 64:1017–20. CaiZ LiuQ Understanding the Global Cancer Statistics 2018: implications for cancer control Sci China Life Sci 2021 64 1017 20 10.1007/s11427-019-9816-131463738 Search in Google Scholar

Wong MCS, Lao XQ, Ho K-F, Goggins WB, Tse SLA. Incidence and mortality of lung cancer: global trends and association with socioeconomic status. Sci Rep. 2017; 7:14300. doi: 10.1038/s41598-017-14513-7 WongMCS LaoXQ HoK-F GogginsWB TseSLA Incidence and mortality of lung cancer: global trends and association with socioeconomic status Sci Rep 2017 7 14300 10.1038/s41598-017-14513-7 566273329085026 Otwórz DOISearch in Google Scholar

Nargis N, Yong H-H, Driezen P, Mbulo L, Zhao L, Fong GT, et al. Socioeconomic patterns of smoking cessation behavior in low and middle-income countries: emerging evidence from the Global Adult Tobacco Surveys and International Tobacco Control Surveys. PLoS One. 2019; 14:e02202232019. doi: 10.1371/journal.pone.0220223 NargisN YongH-H DriezenP MbuloL ZhaoL FongGT Socioeconomic patterns of smoking cessation behavior in low and middle-income countries: emerging evidence from the Global Adult Tobacco Surveys and International Tobacco Control Surveys PLoS One 2019 14 e02202232019 10.1371/journal.pone.0220223 673086931490958 Otwórz DOISearch in Google Scholar

Sonea L, Buse M, Gulei D, Onaciu A, Simon I, Braicu C, Berindan-Neagoe I. Decoding the emerging patterns exhibited in non-coding RNAs characteristic of lung cancer with regard to their clinical significance. Curr Genomics. 2018; 19:258–78. SoneaL BuseM GuleiD OnaciuA SimonI BraicuC Berindan-NeagoeI Decoding the emerging patterns exhibited in non-coding RNAs characteristic of lung cancer with regard to their clinical significance Curr Genomics 2018 19 258 78 10.2174/1389202918666171005100124593044829755289 Search in Google Scholar

Litwin M, Szczepańska-Buda A, Piotrowska A, Dzięgiel P, Witkiewicz W. The meaning of PIWI proteins in cancer development. Oncol Lett. 2017; 13:3354–62. LitwinM Szczepańska-BudaA PiotrowskaA DzięgielP WitkiewiczW The meaning of PIWI proteins in cancer development Oncol Lett 2017 13 3354 62 10.3892/ol.2017.5932543146728529570 Search in Google Scholar

Lin H, Spradling AC. A novel group of pumilio mutations affects the asymmetric division of germline stem cells in the Drosophila ovary. Development. 1997; 124:2463–76. LinH SpradlingAC A novel group of pumilio mutations affects the asymmetric division of germline stem cells in the Drosophila ovary Development 1997 124 2463 76 10.1242/dev.124.12.24639199372 Search in Google Scholar

Gan B, Chen S, Liu H, Min J, Liu K. Structure and function of eTudor domain containing TDRD proteins. Crit Rev Biochem Mol Biol. 2019; 54:119–32. GanB ChenS LiuH MinJ LiuK Structure and function of eTudor domain containing TDRD proteins Crit Rev Biochem Mol Biol 2019 54 119 32 10.1080/10409238.2019.160319931046474 Search in Google Scholar

Huang X, Tóth KF, Aravin AA. piRNA biogenesis in Drosophila melanogaster. Trends Genet. 2017; 33:882–94. HuangX TóthKF AravinAA piRNA biogenesis in Drosophila melanogaster Trends Genet 2017 33 882 94 10.1016/j.tig.2017.09.002577312928964526 Search in Google Scholar

Yu T, Koppetsch BS, Pagliarani S, Johnston S, Silverstein NJ, Luban J, et al. The piRNA response to retroviral invasion of the koala genome. Cell. 2019; 179:632–643.e12. doi: 10.1016/j.cell.2019.09.002 YuT KoppetschBS PagliaraniS JohnstonS SilversteinNJ LubanJ The piRNA response to retroviral invasion of the koala genome Cell 2019 179 632 643.e12 10.1016/j.cell.2019.09.002 680066631607510 Otwórz DOISearch in Google Scholar

Cox DN, Chao A, Baker J, Chang L, Qiao D, Lin H. A novel class of evolutionarily conserved genes defined by piwi are essential for stem cell self-renewal. Genes Dev. 1998; 12:3715–27. CoxDN ChaoA BakerJ ChangL QiaoD LinH A novel class of evolutionarily conserved genes defined by piwi are essential for stem cell self-renewal Genes Dev 1998 12 3715 27 10.1101/gad.12.23.37153172559851978 Search in Google Scholar

Reinke V, Smith HE, Nance J, Wang J, Van Doren C, Begley R, et al. A global profile of germline gene expression in C. elegans. Mol Cell. 2000; 6:605–16. ReinkeV SmithHE NanceJ WangJ Van DorenC BegleyR A global profile of germline gene expression in C. elegans Mol Cell 2000 6 605 16 10.1016/S1097-2765(00)00059-9 Search in Google Scholar

Kuramochi-Miyagawa S, Kimura T, Yomogida K, Kuroiwa A, Tadokoro Y, Fujita Y, et al. Two mouse piwi-related genes: miwi and mili. Mech Dev. 2001; 108:121–33. Kuramochi-MiyagawaS KimuraT YomogidaK KuroiwaA TadokoroY FujitaY Two mouse piwi-related genes: miwi and mili Mech Dev 2001 108 121 33 10.1016/S0925-4773(01)00499-3 Search in Google Scholar

Sharma AK, Nelson MC, Brandt JE, Wessman M, Mahmud N, Weller KP, Hoffman R. Human CD34+ stem cells express the hiwi gene, a human homologue of the Drosophila gene piwi. Blood. 2001; 97:426–34. SharmaAK NelsonMC BrandtJE WessmanM MahmudN WellerKP HoffmanR Human CD34+ stem cells express the hiwi gene, a human homologue of the Drosophila gene piwi Blood 2001 97 426 34 10.1182/blood.V97.2.426 Search in Google Scholar

Qiao D, Zeeman A-M, Deng W, Looijenga LHJ, Lin H. Molecular characterization of hiwi, a human member of the piwi gene family whose overexpression is correlated to seminomas. Oncogene. 2002; 21:3988–99. QiaoD ZeemanA-M DengW LooijengaLHJ LinH Molecular characterization of hiwi, a human member of the piwi gene family whose overexpression is correlated to seminomas Oncogene 2002 21 3988 99 10.1038/sj.onc.1205505 Search in Google Scholar

Mochizuki K, Fine NA, Fujisawa T, Gorovsky MA. Analysis of a piwi-related gene implicates small RNAs in genome rearrangement in Tetrahymena. Cell. 2002; 110:689–99. MochizukiK FineNA FujisawaT GorovskyMA Analysis of a piwi-related gene implicates small RNAs in genome rearrangement in Tetrahymena Cell 2002 110 689 99 10.1016/S0092-8674(02)00909-1 Search in Google Scholar

Tan CH, Lee TC, Weeraratne SD, Korzh V, Lim TM, Gong Z. Ziwi, the zebrafish homologue of the Drosophila piwi: co-localization with vasa at the embryonic genital ridge and gonad-specific expression in the adults. Mech Dev. 2002; 119(Suppl 1):S221–4. TanCH LeeTC WeeraratneSD KorzhV LimTM GongZ Ziwi, the zebrafish homologue of the Drosophila piwi: co-localization with vasa at the embryonic genital ridge and gonad-specific expression in the adults Mech Dev 2002 119 Suppl 1 S221 4 10.1016/S0925-4773(03)00120-5 Search in Google Scholar

Girard A, Sachidanandam R, Hannon GJ, Carmell MA. A germline-specific class of small RNAs binds mammalian Piwi proteins. Nature. 2006; 442(7099):199–202. GirardA SachidanandamR HannonGJ CarmellMA A germline-specific class of small RNAs binds mammalian Piwi proteins Nature 2006 442 7099 199 202 10.1038/nature0491716751776 Search in Google Scholar

Lee JH, Schütte D, Wulf G, Füzesi L, Radzun HJ, Schweyer S, et al. Stem-cell protein Piwil2 is widely expressed in tumors and inhibits apoptosis through activation of Stat3/Bcl-XL pathway. Human Mol Genet. 2005; 15:201–11. LeeJH SchütteD WulfG FüzesiL RadzunHJ SchweyerS Stem-cell protein Piwil2 is widely expressed in tumors and inhibits apoptosis through activation of Stat3/Bcl-XL pathway Human Mol Genet 2005 15 201 11 10.1093/hmg/ddi43016377660 Search in Google Scholar

Liu X, Sun Y, Guo J, Ma H, Li J, Dong B, et al. Expression of hiwi gene in human gastric cancer was associated with proliferation of cancer cells. Int J Cancer. 2006; 118:1922–9. LiuX SunY GuoJ MaH LiJ DongB Expression of hiwi gene in human gastric cancer was associated with proliferation of cancer cells Int J Cancer 2006 118 1922 9 10.1002/ijc.2157516287078 Search in Google Scholar

Taubert H, Greither T, Kaushal D, Würl P, Bache M, Bartel F, et al. Expression of the stem cell self-renewal gene Hiwi and risk of tumour-related death in patients with soft-tissue sarcoma. Oncogene. 2007; 26:1098–100. TaubertH GreitherT KaushalD WürlP BacheM BartelF Expression of the stem cell self-renewal gene Hiwi and risk of tumour-related death in patients with soft-tissue sarcoma Oncogene 2007 26 1098 100 10.1038/sj.onc.120988016953229 Search in Google Scholar

Grochola LF, Greither T, Taubert H, Möller P, Knippschild U, Udelnow A, et al. The stem cell-associated Hiwi gene in human adenocarcinoma of the pancreas: expression and risk of tumour-related death. Br J Cancer. 2008; 99:1083–8. GrocholaLF GreitherT TaubertH MöllerP KnippschildU UdelnowA The stem cell-associated Hiwi gene in human adenocarcinoma of the pancreas: expression and risk of tumour-related death Br J Cancer 2008 99 1083 8 10.1038/sj.bjc.6604653256707218781170 Search in Google Scholar

He W, Wang Z, Wang Q, Fan Q, Shou C, Wang J, et al. Expression of HIWI in human esophageal squamous cell carcinoma is significantly associated with poorer prognosis. BMC Cancer. 2009; 9:426. doi: 10.1186/1471-2407-9-426 HeW WangZ WangQ FanQ ShouC WangJ Expression of HIWI in human esophageal squamous cell carcinoma is significantly associated with poorer prognosis BMC Cancer 2009 9 426 10.1186/1471-2407-9-426 280151919995427 Otwórz DOISearch in Google Scholar

He G, Chen L, Ye Y, Xiao Y, Hua K, Jarjoura D, et al. Piwil2 expressed in various stages of cervical neoplasia is a potential complementary marker for p16INK4a. Am J Transl Res. 2010; 2:156–69. HeG ChenL YeY XiaoY HuaK JarjouraD Piwil2 expressed in various stages of cervical neoplasia is a potential complementary marker for p16INK4a Am J Transl Res 2010 2 156 69 Search in Google Scholar

Liu JJ, Shen R, Chen L, Ye Y, He G, Hua K, et al. Piwil2 is expressed in various stages of breast cancers and has the potential to be used as a novel biomarker. Int J Clin Exp Pathol. 2010; 3:328–37. LiuJJ ShenR ChenL YeY HeG HuaK Piwil2 is expressed in various stages of breast cancers and has the potential to be used as a novel biomarker Int J Clin Exp Pathol 2010 3 328 37 Search in Google Scholar

Sun G, Wang Y, Sun L, Luo H, Liu N, Fu Z, You Y. Clinical significance of Hiwi gene expression in gliomas. Brain Res. 2011; 1373:183–8. SunG WangY SunL LuoH LiuN FuZ YouY Clinical significance of Hiwi gene expression in gliomas Brain Res 2011 1373 183 8 10.1016/j.brainres.2010.11.09721138738 Search in Google Scholar

Cheng J, Guo J-M, Xiao B-X, Miao Y, Jiang Z, Zhou H, Li Q-N. piRNA, the new non-coding RNA, is aberrantly expressed in human cancer cells. Clin Chim Acta. 2011; 412:1621–5. ChengJ GuoJ-M XiaoB-X MiaoY JiangZ ZhouH LiQ-N piRNA, the new non-coding RNA, is aberrantly expressed in human cancer cells Clin Chim Acta 2011 412 1621 5 10.1016/j.cca.2011.05.01521616063 Search in Google Scholar

Yan ZE, Qu L-k, Lin M, Liu C-y, Bin D, Xing X-f, et al. HIWI expression profile in cancer cells and its prognostic value for patients with colorectal cancer. Chinese Med J (Engl). 2011; 124:2144–9. YanZE QuL-k LinM LiuC-y BinD XingX-f HIWI expression profile in cancer cells and its prognostic value for patients with colorectal cancer Chinese Med J (Engl) 2011 124 2144 9 Search in Google Scholar

Cheng J, Deng H, Xiao B, Zhou H, Zhou F, Shen Z, Guo J. piR-823, a novel non-coding small RNA, demonstrates in vitro and in vivo tumor suppressive activity in human gastric cancer cells. Cancer Lett. 2012; 315:12–7. ChengJ DengH XiaoB ZhouH ZhouF ShenZ GuoJ piR-823, a novel non-coding small RNA, demonstrates in vitro and in vivo tumor suppressive activity in human gastric cancer cells Cancer Lett 2012 315 12 7 10.1016/j.canlet.2011.10.00422047710 Search in Google Scholar

Li D, Sun X, Yan D, Huang J, Luo Q, Tang H, Peng Z. Piwil2 modulates the proliferation and metastasis of colon cancer via regulation of matrix metallopeptidase 9 transcriptional activity. Exp Biol Med (Maywood). 2012; 237:1231–40. LiD SunX YanD HuangJ LuoQ TangH PengZ Piwil2 modulates the proliferation and metastasis of colon cancer via regulation of matrix metallopeptidase 9 transcriptional activity Exp Biol Med (Maywood) 2012 237 1231 40 10.1258/ebm.2012.01138023104504 Search in Google Scholar

Chen C, Liu J, Xu G. Overexpression of PIWI proteins in human stage III epithelial ovarian cancer with lymph node metastasis. Cancer Biomark. 2013; 13:315–21. ChenC LiuJ XuG Overexpression of PIWI proteins in human stage III epithelial ovarian cancer with lymph node metastasis Cancer Biomark 2013 13 315 21 10.3233/CBM-13036024440970 Search in Google Scholar

Zhang H, Ren Y, Xu H, Pang D, Duan C, Liu C. The expression of stem cell protein Piwil2 and piR-932 in breast cancer. Surg Oncol. 2013; 22:217–23. ZhangH RenY XuH PangD DuanC LiuC The expression of stem cell protein Piwil2 and piR-932 in breast cancer Surg Oncol 2013 22 217 23 10.1016/j.suronc.2013.07.00123992744 Search in Google Scholar

Wang D-W, Wang Z-H, Wang L-L, Song Y, Zhang G-Z. Overexpression of hiwi promotes growth of human breast cancer cells. Asian Pac J Cancer Prev. 2014; 15:7553–8. WangD-W WangZ-H WangL-L SongY ZhangG-Z Overexpression of hiwi promotes growth of human breast cancer cells Asian Pac J Cancer Prev 2014 15 7553 8 10.7314/APJCP.2014.15.18.7553 Search in Google Scholar

Yan H, Wu Q-L, Sun C-Y, Ai L-S, Deng J, Zhang L, et al. piRNA-823 contributes to tumorigenesis by regulating de novo DNA methylation and angiogenesis in multiple myeloma. Leukemia. 2015; 29:196–206. YanH WuQ-L SunC-Y AiL-S DengJ ZhangL piRNA-823 contributes to tumorigenesis by regulating de novo DNA methylation and angiogenesis in multiple myeloma Leukemia 2015 29 196 206 10.1038/leu.2014.13524732595 Search in Google Scholar

Al-Janabi O, Wach S, Nolte E, Weigelt K, Rau TT, Stöhr C, et al. Piwi-like 1 and 4 gene transcript levels are associated with clinicopathological parameters in renal cell carcinomas. Biochim Biophys Acta. 2014; 1842:686–90. Al-JanabiO WachS NolteE WeigeltK RauTT StöhrC Piwi-like 1 and 4 gene transcript levels are associated with clinicopathological parameters in renal cell carcinomas Biochim Biophys Acta 2014 1842 686 90 10.1016/j.bbadis.2014.01.01424509249 Search in Google Scholar

Liu W, Gao Q, Chen K, Xue X, Li M, Chen Q, et al. Hiwi facilitates chemoresistance as a cancer stem cell marker in cervical cancer. Oncol Rep. 2014; 32:1853–60. LiuW GaoQ ChenK XueX LiM ChenQ Hiwi facilitates chemoresistance as a cancer stem cell marker in cervical cancer Oncol Rep 2014 32 1853 60 10.3892/or.2014.340125119492 Search in Google Scholar

Xie Y, Yang Y, Ji D, Zhang D, Yao X, Zhang X. Hiwi downregulation, mediated by shRNA, reduces the proliferation and migration of human hepatocellular carcinoma cells. Mol Med Rep. 2014; 11:1455–61. XieY YangY JiD ZhangD YaoX ZhangX Hiwi downregulation, mediated by shRNA, reduces the proliferation and migration of human hepatocellular carcinoma cells Mol Med Rep 2014 11 1455 61 10.3892/mmr.2014.284725370791 Search in Google Scholar

Chu H, Hui G, Yuan L, Shi D, Wang Y, Du M, et al. Identification of novel piRNAs in bladder cancer. Cancer Lett. 2015; 356:561–7. ChuH HuiG YuanL ShiD WangY DuM Identification of novel piRNAs in bladder cancer Cancer Lett 2015 356 561 7 10.1016/j.canlet.2014.10.00425305452 Search in Google Scholar

Fu A, Jacobs DI, Hoffman AE, Zheng T, Zhu Y. PIWI-interacting RNA 021285 is involved in breast tumorigenesis possibly by remodeling the cancer epigenome. Carcinogenesis. 2015; 36:1094–102. FuA JacobsDI HoffmanAE ZhengT ZhuY PIWI-interacting RNA 021285 is involved in breast tumorigenesis possibly by remodeling the cancer epigenome Carcinogenesis 2015 36 1094 102 10.1093/carcin/bgv105500615226210741 Search in Google Scholar

Yang Y, Zhang X, Song D, Wei J. Piwil2 modulates the invasion and metastasis of prostate cancer by regulating the expression of matrix metalloproteinase-9 and epithelial-mesenchymal transitions. Oncol Lett. 2015; 10:1735–40. YangY ZhangX SongD WeiJ Piwil2 modulates the invasion and metastasis of prostate cancer by regulating the expression of matrix metalloproteinase-9 and epithelial-mesenchymal transitions Oncol Lett 2015 10 1735 40 10.3892/ol.2015.3392453327926622742 Search in Google Scholar

Müller S, Raulefs S, Bruns P, Afonso-Grunz F, Plötner A, Thermann R, et al. Next-generation sequencing reveals novel differentially regulated mRNAs, lncRNAs, miRNAs, sdRNAs and a piRNA in pancreatic cancer. Mol Cancer. 2015; 14:94. doi: 10.1186/s12943-015-0358-5 MüllerS RaulefsS BrunsP Afonso-GrunzF PlötnerA ThermannR Next-generation sequencing reveals novel differentially regulated mRNAs, lncRNAs, miRNAs, sdRNAs and a piRNA in pancreatic cancer Mol Cancer 2015 14 94 10.1186/s12943-015-0358-5 441753625910082 Otwórz DOISearch in Google Scholar

Chu H, Xia L, Qiu X, Gu D, Zhu L, Jin J, et al. Genetic variants in noncoding PIWI-interacting RNA and colorectal cancer risk. Cancer. 2015; 121:2044–52. ChuH XiaL QiuX GuD ZhuL JinJ Genetic variants in noncoding PIWI-interacting RNA and colorectal cancer risk Cancer 2015 121 2044 52 10.1002/cncr.2931425740697 Search in Google Scholar

Wang Y, Jiang Y, Ma N, Sang B, Hu X, Cong X, Liu Z. Overexpression of Hiwi inhibits the growth and migration of chronic myeloid leukemia cells. Cell Biochem Biophys. 2015; 73:117–24. WangY JiangY MaN SangB HuX CongX LiuZ Overexpression of Hiwi inhibits the growth and migration of chronic myeloid leukemia cells Cell Biochem Biophys 2015 73 117 24 10.1007/s12013-015-0651-325701408 Search in Google Scholar

Chen YJ, Xiong XF, Wen SQ, Tian L, Cheng WL, Qi YQ. Expression and clinical significance of PIWIL2 in hilar cholangiocarcinoma tissues and cell lines. Genet Mol Res. 2015; 14:7053–61. ChenYJ XiongXF WenSQ TianL ChengWL QiYQ Expression and clinical significance of PIWIL2 in hilar cholangiocarcinoma tissues and cell lines Genet Mol Res 2015 14 7053 61 10.4238/2015.June.26.1526125915 Search in Google Scholar

Busch J, Ralla B, Jung M, Wotschofsky Z, Trujillo-Arribas E, Schwabe P, et al. Piwi-interacting RNAs as novel prognostic markers in clear cell renal cell carcinomas. J Exp Clin Cancer Res. 2015; 34:61. doi: 10.1186/s13046-015-0180-3 BuschJ RallaB JungM WotschofskyZ Trujillo-ArribasE SchwabeP Piwi-interacting RNAs as novel prognostic markers in clear cell renal cell carcinomas J Exp Clin Cancer Res 2015 34 61 10.1186/s13046-015-0180-3 446720526071182 Otwórz DOISearch in Google Scholar

Chen Z, Che Q, Jiang F-Z, Wang H-H, Wang F-Y, Liao Y, Wan X-P. Piwil1 causes epigenetic alteration of PTEN gene via upregulation of DNA methyltransferase in type I endometrial cancer. Biochem Biophys Res Commun. 2015; 463:876–80. ChenZ CheQ JiangF-Z WangH-H WangF-Y LiaoY WanX-P Piwil1 causes epigenetic alteration of PTEN gene via upregulation of DNA methyltransferase in type I endometrial cancer Biochem Biophys Res Commun 2015 463 876 80 10.1016/j.bbrc.2015.06.02826056945 Search in Google Scholar

Taubert H, Wach S, Jung R, Pugia M, Keck B, Bertz S, et al. Piwil 2 expression is correlated with disease-specific and progression-free survival of chemotherapy-treated bladder cancer patients. Mol Med. 2015; 21:371–80. TaubertH WachS JungR PugiaM KeckB BertzS Piwil 2 expression is correlated with disease-specific and progression-free survival of chemotherapy-treated bladder cancer patients Mol Med 2015 21 371 80 10.2119/molmed.2014.00250453447425998509 Search in Google Scholar

Wang Z, Liu N, Shi S, Liu S, Lin H. The role of PIWIL4, an Argonaute family protein, in breast cancer. J Biol Chem. 2016; 291:10646–58. WangZ LiuN ShiS LiuS LinH The role of PIWIL4, an Argonaute family protein, in breast cancer J Biol Chem 2016 291 10646 58 10.1074/jbc.M116.723239486591326957540 Search in Google Scholar

Firmino N, Martinez VD, Rowbotham DA, Enfield KS, Bennewith KL, Lam WL. HPV status is associated with altered PIWI-interacting RNA expression pattern in head and neck cancer. Oral Oncol. 2016; 55:43–8. FirminoN MartinezVD RowbothamDA EnfieldKS BennewithKL LamWL HPV status is associated with altered PIWI-interacting RNA expression pattern in head and neck cancer Oral Oncol 2016 55 43 8 10.1016/j.oraloncology.2016.01.012480843926852287 Search in Google Scholar

Jacobs DI, Qin Q, Lerro MC, Fu A, Dubrow R, Claus EB, et al. PIWI-interacting RNAs in gliomagenesis: evidence from post-GWAS and functional analyses. Cancer Epidemiol Biomarkers Prev. 2016; 25:1073–80. JacobsDI QinQ LerroMC FuA DubrowR ClausEB PIWI-interacting RNAs in gliomagenesis: evidence from post-GWAS and functional analyses Cancer Epidemiol Biomarkers Prev 2016 25 1073 80 10.1158/1055-9965.EPI-16-004727197292 Search in Google Scholar

Gambichler T, Kohsik C, Höh AK, Lang K, Käfferlein HU, Brüning T, et al. Expression of PIWIL3 in primary and metastatic melanoma. J Cancer Res Clin Oncol. 2017; 143:433–7. GambichlerT KohsikC HöhAK LangK KäfferleinHU BrüningT Expression of PIWIL3 in primary and metastatic melanoma J Cancer Res Clin Oncol 2017 143 433 7 10.1007/s00432-016-2305-227858163 Search in Google Scholar

Sivagurunathan S, Arunachalam JP, Chidambaram S. PIWI-like protein, HIWI2 is aberrantly expressed in retinoblastoma cells and affects cell-cycle potentially through OTX2. Cell Mol Biol Lett. 2017; 22:17. doi: 10.1186/s11658-017-0048-y SivagurunathanS ArunachalamJP ChidambaramS PIWI-like protein, HIWI2 is aberrantly expressed in retinoblastoma cells and affects cell-cycle potentially through OTX2 Cell Mol Biol Lett 2017 22 17 10.1186/s11658-017-0048-y 557609528861107 Otwórz DOISearch in Google Scholar

Vychytilova-Faltejskova P, Stitkovcova K, Radova L, Sachlova M, Kosarova Z, Slaba K, et al. Circulating PIWI-interacting RNAs piR-5937 and piR-28876 are promising diagnostic biomarkers of colon cancer. Cancer Epidemiol Biomarkers Prev. 2018; 27:1019–28. Vychytilova-FaltejskovaP StitkovcovaK RadovaL SachlovaM KosarovaZ SlabaK Circulating PIWI-interacting RNAs piR-5937 and piR-28876 are promising diagnostic biomarkers of colon cancer Cancer Epidemiol Biomarkers Prev 2018 27 1019 28 10.1158/1055-9965.EPI-18-031829976566 Search in Google Scholar

Jacobs DI, Qin Q, Fu A, Chen Z, Zhou J, Zhu Y. piRNA-8041 is downregulated in human glioblastoma and suppresses tumor growth in vitro and in vivo. Oncotarget. 2018; 9:37616–26. JacobsDI QinQ FuA ChenZ ZhouJ ZhuY piRNA-8041 is downregulated in human glioblastoma and suppresses tumor growth in vitro and in vivo Oncotarget 2018 9 37616 26 10.18632/oncotarget.26331634088530701019 Search in Google Scholar

Gao C-L, Sun R, Li D-H, Gong F. PIWI-like protein 1 upregulation promotes gastric cancer invasion and metastasis. Onco Targets Ther. 2018; 11:8783–89. GaoC-L SunR LiD-H GongF PIWI-like protein 1 upregulation promotes gastric cancer invasion and metastasis Onco Targets Ther 2018 11 8783 89 10.2147/OTT.S186827628751230584336 Search in Google Scholar

Eckstein M, Jung R, Weigelt K, Sikic D, Stöhr R, Geppert C, et al. Piwi-like 1 and-2 protein expression levels are prognostic factors for muscle invasive urothelial bladder cancer patients. Sci Rep. 2018; 8:17693. doi: 10.1038/s41598-018-35637-4 EcksteinM JungR WeigeltK SikicD StöhrR GeppertC Piwi-like 1 and-2 protein expression levels are prognostic factors for muscle invasive urothelial bladder cancer patients Sci Rep 2018 8 17693 10.1038/s41598-018-35637-4 628383830523270 Otwórz DOISearch in Google Scholar

Heng ZS, Lee JY, Subhramanyam CS, Wang C, Thanga LZ, Hu Q. The role of 17β-estradiol-induced upregulation of Piwi-like 4 in modulating gene expression and motility in breast cancer cells. Oncol Rep. 2018; 40:2525–35. HengZS LeeJY SubhramanyamCS WangC ThangaLZ HuQ The role of 17β-estradiol-induced upregulation of Piwi-like 4 in modulating gene expression and motility in breast cancer cells Oncol Rep 2018 40 2525 35 10.3892/or.2018.6676615187830226541 Search in Google Scholar

Li B, Hong J, Hong M, Wang Y, Yu T, Zang S, Wu Q. piRNA-823 delivered by multiple myeloma-derived extracellular vesicles promoted tumorigenesis through re-educating endothelial cells in the tumor environment. Oncogene. 2019; 38:5227–38. LiB HongJ HongM WangY YuT ZangS WuQ piRNA-823 delivered by multiple myeloma-derived extracellular vesicles promoted tumorigenesis through re-educating endothelial cells in the tumor environment Oncogene 2019 38 5227 38 10.1038/s41388-019-0788-430890754 Search in Google Scholar

Roy J, Das B, Jain N, Mallick B. PIWI-interacting RNA 39980 promotes tumor progression and reduces drug sensitivity in neuroblastoma cells. J Cell Physiol. 2020; 235:2286–99. RoyJ DasB JainN MallickB PIWI-interacting RNA 39980 promotes tumor progression and reduces drug sensitivity in neuroblastoma cells J Cell Physiol 2020 235 2286 99 10.1002/jcp.2913631478570 Search in Google Scholar

Tan L, Mai D, Zhang B, Jiang X, Zhang J, Bai R, et al. PIWI-interacting RNA-36712 restrains breast cancer progression and chemoresistance by interaction with SEPW1 pseudogene SEPW1P RNA. Mol Cancer. 2019; 18:9. doi: 10.1186/s12943-019-0940-3 TanL MaiD ZhangB JiangX ZhangJ BaiR PIWI-interacting RNA-36712 restrains breast cancer progression and chemoresistance by interaction with SEPW1 pseudogene SEPW1P RNA Mol Cancer 2019 18 9 10.1186/s12943-019-0940-3 633050130636640 Otwórz DOISearch in Google Scholar

Lin Y, Holden V, Dhilipkannah P, Deepak J, Todd NW, Jiang F. A non-coding RNA landscape of bronchial epitheliums of lung cancer patients. Biomedicines. 2020; 8:88. doi: 10.3390/biomedicines8040088 LinY HoldenV DhilipkannahP DeepakJ ToddNW JiangF A non-coding RNA landscape of bronchial epitheliums of lung cancer patients Biomedicines 2020 8 88 10.3390/biomedicines8040088 723574432294932 Otwórz DOISearch in Google Scholar

Liu Y, Dong Y, He X, Gong A, Gao J, Hao X, et al. piR-hsa-211106 inhibits the progression of lung adenocarcinoma through pyruvate carboxylase and enhances chemotherapy sensitivity. Front Oncol. 2021; 11:651915. doi: 10.3389/fonc.2021.651915 LiuY DongY HeX GongA GaoJ HaoX piR-hsa-211106 inhibits the progression of lung adenocarcinoma through pyruvate carboxylase and enhances chemotherapy sensitivity Front Oncol 2021 11 651915. 10.3389/fonc.2021.651915 826094334249688 Otwórz DOISearch in Google Scholar

Li J, Wang N, Zhang F, Jin S, Dong Y, Dong X, et al. PIWI-interacting RNAs are aberrantly expressed and may serve as novel biomarkers for diagnosis of lung adenocarcinoma. Thorac Cancer. 2021; 12:2468–77. LiJ WangN ZhangF JinS DongY DongX PIWI-interacting RNAs are aberrantly expressed and may serve as novel biomarkers for diagnosis of lung adenocarcinoma Thorac Cancer 2021 12 2468 77 10.1111/1759-7714.14094844790534346164 Search in Google Scholar

Fathizadeh H, Asemi Z. Epigenetic roles of PIWI proteins and piRNAs in lung cancer. Cell Biosci. 2019; 9:102. doi: 10.1186/s13578-019-0368-x FathizadehH AsemiZ Epigenetic roles of PIWI proteins and piRNAs in lung cancer Cell Biosci 2019 9 102 10.1186/s13578-019-0368-x 692584231890151 Otwórz DOISearch in Google Scholar

Dana PM, Mansournia MA, Mirhashemi SM. PIWI-interacting RNAs: new biomarkers for diagnosis and treatment of breast cancer. Cell Biosci. 2020; 10:44. doi: 10.1186/s13578-020-00403-5 DanaPM MansourniaMA MirhashemiSM PIWI-interacting RNAs: new biomarkers for diagnosis and treatment of breast cancer Cell Biosci 2020 10 44 10.1186/s13578-020-00403-5 709245632211149 Otwórz DOISearch in Google Scholar

Yu Y, Xiao J, Hann SS. The emerging roles of PIWI-interacting RNA in human cancers. Cancer Manag Res. 2019; 11:5895–909. YuY XiaoJ HannSS The emerging roles of PIWI-interacting RNA in human cancers Cancer Manag Res 2019 11 5895 909 10.2147/CMAR.S209300661201731303794 Search in Google Scholar

Sokolova OA, Ilyin AA, Poltavets AS, Nenasheva VV, Mikhaleva EA, Shevelyov YY, Klenov MS. Yb body assembly on the flamenco piRNA precursor transcripts reduces genic piRNA production. Mol Biol Cell. 2019; 30:1544–54. SokolovaOA IlyinAA PoltavetsAS NenashevaVV MikhalevaEA ShevelyovYY KlenovMS Yb body assembly on the flamenco piRNA precursor transcripts reduces genic piRNA production Mol Biol Cell 2019 30 1544 54 10.1091/mbc.E17-10-0591672469530943101 Search in Google Scholar

Ishizu H, Kinoshita T, Hirakata S, Komatsuzaki C, Siomi MC. Distinct and collaborative functions of Yb and Armitage in transposon-targeting piRNA biogenesis. Cell Rep. 2019; 27:1822-35.e8. doi: 10.1016/j.celrep.2019.04.029. IshizuH KinoshitaT HirakataS KomatsuzakiC SiomiMC Distinct and collaborative functions of Yb and Armitage in transposon-targeting piRNA biogenesis Cell Rep 2019 27 1822 35.e8 10.1016/j.celrep.2019.04.029 31067466 Otwórz DOISearch in Google Scholar

Saito K, Inagaki S, Mituyama T, Kawamura Y, Ono Y, Sakota E, et al. A regulatory circuit for piwi by the large Maf gene traffic jam in Drosophila. Nature. 2009; 461:1296–9. SaitoK InagakiS MituyamaT KawamuraY OnoY SakotaE A regulatory circuit for piwi by the large Maf gene traffic jam in Drosophila Nature 2009 461 1296 9 10.1038/nature0850119812547 Search in Google Scholar

Aguiar ERGR, de Almeida JPP, Queiroz LR, Oliveira LS, Olmo RP, de Faria IJDS, et al. A single unidirectional piRNA cluster similar to the flamenco locus is the major source of EVE-derived transcription and small RNAs in Aedes aegypti mosquitoes. RNA. 2020; 26:581–94. AguiarERGR de AlmeidaJPP QueirozLR OliveiraLS OlmoRP de FariaIJDS A single unidirectional piRNA cluster similar to the flamenco locus is the major source of EVE-derived transcription and small RNAs in Aedes aegypti mosquitoes RNA 2020 26 581 94 10.1261/rna.073965.119716135431996404 Search in Google Scholar

Le Thomas A, Rogers AK, Webster A, Marinov GK, Liao SE, Perkins EM, et al. Piwi induces piRNA-guided transcriptional silencing and establishment of a repressive chromatin state. Genes Dev. 2013; 27:390–9. Le ThomasA RogersAK WebsterA MarinovGK LiaoSE PerkinsEM Piwi induces piRNA-guided transcriptional silencing and establishment of a repressive chromatin state Genes Dev 2013 27 390 9 10.1101/gad.209841.112358955623392610 Search in Google Scholar

Chen P, Luo Y, Aravin AA. RDC complex executes a dynamic piRNA program during Drosophila spermatogenesis to safeguard male fertility. PLoS Genet. 2021; 17:e1009591. doi: 10.1371/journal.pgen.1009591 ChenP LuoY AravinAA RDC complex executes a dynamic piRNA program during Drosophila spermatogenesis to safeguard male fertility PLoS Genet 2021 17 e1009591 10.1371/journal.pgen.1009591 841236434473737 Otwórz DOISearch in Google Scholar

Qi H, Watanabe T, Ku H-Y, Liu N, Zhong M, Lin H. The Yb body, a major site for Piwi-associated RNA biogenesis and a gateway for Piwi expression and transport to the nucleus in somatic cells. J Biol Chem. 2011; 286:3789–97. QiH WatanabeT KuH-Y LiuN ZhongM LinH The Yb body, a major site for Piwi-associated RNA biogenesis and a gateway for Piwi expression and transport to the nucleus in somatic cells J Biol Chem 2011 286 3789 97 10.1074/jbc.M110.193888303038021106531 Search in Google Scholar

Pane A, Wehr K, Schüpbach T. zucchini and squash encode two putative nucleases required for rasiRNA production in the Drosophila germline. Dev Cell. 2007; 12:851–62. PaneA WehrK SchüpbachT zucchini and squash encode two putative nucleases required for rasiRNA production in the Drosophila germline Dev Cell 2007 12 851 62 10.1016/j.devcel.2007.03.022194581417543859 Search in Google Scholar

Olivieri D, Senti K-A, Subramanian S, Sachidanandam R, Brennecke J. The cochaperone shutdown defines a group of biogenesis factors essential for all piRNA populations in Drosophila. Mol Cell. 2012; 47:954–69. OlivieriD SentiK-A SubramanianS SachidanandamR BrenneckeJ The cochaperone shutdown defines a group of biogenesis factors essential for all piRNA populations in Drosophila Mol Cell 2012 47 954 69 10.1016/j.molcel.2012.07.021346380522902557 Search in Google Scholar

Xie W, Sowemimo I, Hayashi R, Wang J, Burkard TR, Brennecke J, et al. Structure-function analysis of microRNA 3′-end trimming by Nibbler. Proc Natl Acad Sci U S A. 2020; 117:30370–79. XieW SowemimoI HayashiR WangJ BurkardTR BrenneckeJ Structure-function analysis of microRNA 3′-end trimming by Nibbler Proc Natl Acad Sci U S A 2020 117 30370 79 10.1073/pnas.2018156117772015333199607 Search in Google Scholar

Ding D, Chen C. Zucchini: the key ingredient to unveil piRNA precursor processing. Biol Reprod. 2020; 103:452–54. DingD ChenC Zucchini: the key ingredient to unveil piRNA precursor processing Biol Reprod 2020 103 452 54 10.1093/biolre/ioaa090744277532524138 Search in Google Scholar

Pippadpally S, Venkatesh T. Deciphering piRNA biogenesis through cytoplasmic granules, mitochondria and exosomes. Arch Biochem Biophys. 2020; 695:108597. doi: 10.1016/j.abb.2020.108597 PippadpallyS VenkateshT Deciphering piRNA biogenesis through cytoplasmic granules, mitochondria and exosomes Arch Biochem Biophys 2020 695 108597 10.1016/j.abb.2020.108597 32976825 Otwórz DOISearch in Google Scholar

Sokolova OA, Iakushev EIu, Stoliarenko AD, Mikhaleva EA, Gvozdev VA, Klenov MS. [The interplay of transposon silencing genes in the Drosophila melanogaster germline]. Mol Biol (Mosk). 2011; 45:633–41. [in Russian, English abstract] SokolovaOA IakushevEIu StoliarenkoAD MikhalevaEA GvozdevVA KlenovMS [The interplay of transposon silencing genes in the Drosophila melanogaster germline] Mol Biol (Mosk) 2011 45 633 41 [in Russian, English abstract] 10.1134/S0026893311030174 Search in Google Scholar

Ozata DM, Gainetdinov I, Zoch A, O’Carroll D, Zamore PD. PIWI-interacting RNAs: small RNAs with big functions. Nat Rev Genet. 2019; 20:89–108. OzataDM GainetdinovI ZochA O’CarrollD ZamorePD PIWI-interacting RNAs: small RNAs with big functions Nat Rev Genet 2019 20 89 108 10.1038/s41576-018-0073-330446728 Search in Google Scholar

Russell SJ, LaMarre J. Transposons and the PIWI pathway: genome defense in gametes and embryos. Reproduction. 2018; 156:R111–24. RussellSJ LaMarreJ Transposons and the PIWI pathway: genome defense in gametes and embryos Reproduction 2018 156 R111 24 10.1530/REP-18-021830037984 Search in Google Scholar

Aravin AA, Sachidanandam R, Girard A, Fejes-Toth K, Hannon GJ. Developmentally regulated piRNA clusters implicate MILI in transposon control. Science. 2007; 316:744–7. AravinAA SachidanandamR GirardA Fejes-TothK HannonGJ Developmentally regulated piRNA clusters implicate MILI in transposon control Science 2007 316 744 7 10.1126/science.114261217446352 Search in Google Scholar

Pal-Bhadra M, Leibovitch BA, Gandhi SG, Chikka MR, Bhadra U, Birchler JA, Elgin SCR. Heterochromatic silencing and HP1 localization in Drosophila are dependent on the RNAi machinery. Science. 2004; 303:669–72. Pal-BhadraM LeibovitchBA GandhiSG ChikkaMR BhadraU BirchlerJA ElginSCR Heterochromatic silencing and HP1 localization in Drosophila are dependent on the RNAi machinery Science 2004 303 669 72 10.1126/science.109265314752161 Search in Google Scholar

Teo RYW, Anand A, Sridhar V, Okamura K, Kai T. Heterochromatin protein 1a functions for piRNA biogenesis predominantly from pericentric and telomeric regions in Drosophila. Nat Commun. 2018; 9:1735. doi: 10.1038/s41467-018-03908-3 TeoRYW AnandA SridharV OkamuraK KaiT Heterochromatin protein 1a functions for piRNA biogenesis predominantly from pericentric and telomeric regions in Drosophila Nat Commun 2018 9 1735 10.1038/s41467-018-03908-3 593567329728561 Otwórz DOISearch in Google Scholar

Zhao K, Cheng S, Miao N, Xu P, Lu X, Zhang Y, et al. A Pandas complex adapted for piRNA-guided transcriptional silencing and heterochromatin formation. Nat Cell Biol. 2019; 21:1261–72. ZhaoK ChengS MiaoN XuP LuX ZhangY A Pandas complex adapted for piRNA-guided transcriptional silencing and heterochromatin formation Nat Cell Biol 2019 21 1261 72 10.1038/s41556-019-0396-031570835 Search in Google Scholar

Watanabe T, Tomizawa SI, Mitsuya K, Totoki Y, Yamamoto Y, Kuramochi-Miyagawa S, et al. Role for piRNAs and noncoding RNA in de novo DNA methylation of the imprinted mouse Rasgrf1 locus. Science. 2011; 332:848–52. WatanabeT TomizawaSI MitsuyaK TotokiY YamamotoY Kuramochi-MiyagawaS Role for piRNAs and noncoding RNA in de novo DNA methylation of the imprinted mouse Rasgrf1 locus Science 2011 332 848 52 10.1126/science.1203919336850721566194 Search in Google Scholar

Théron E, Maupetit-Mehouas S, Pouchin P, Baudet L, Brasset E, Vaury C. The interplay between the Argonaute proteins Piwi and Aub within Drosophila germarium is critical for oogenesis, piRNA biogenesis and TE silencing. Nucleic Acids Res. 2018; 46:10052–65. ThéronE Maupetit-MehouasS PouchinP BaudetL BrassetE VauryC The interplay between the Argonaute proteins Piwi and Aub within Drosophila germarium is critical for oogenesis, piRNA biogenesis and TE silencing Nucleic Acids Res 2018 46 10052 65 10.1093/nar/gky695621271430113668 Search in Google Scholar

Zhang Y, Liu W, Li R, Gu J, Wu P, Peng C, et al. Structural insights into the sequence-specific recognition of Piwi by Drosophila Papi. Proc Natl Acad Sci U S A. 2018; 115:3374–79. ZhangY LiuW LiR GuJ WuP PengC Structural insights into the sequence-specific recognition of Piwi by Drosophila Papi Proc Natl Acad Sci U S A 2018 115 3374 79 10.1073/pnas.1717116115587967229531043 Search in Google Scholar

Wenda JM, Homolka D, Yang Z, Spinelli P, Sachidanandam R, Pandey RR, Pillai RS. Distinct roles of RNA helicases MVH and TDRD9 in PIWI slicing-triggered mammalian piRNA biogenesis and function. Dev Cell. 2017; 41:623–637.e9. doi: 10.1016/j.devcel.2017.05.021 WendaJM HomolkaD YangZ SpinelliP SachidanandamR PandeyRR PillaiRS Distinct roles of RNA helicases MVH and TDRD9 in PIWI slicing-triggered mammalian piRNA biogenesis and function Dev Cell 2017 41 623 637.e9 10.1016/j.devcel.2017.05.021 548118628633017 Otwórz DOISearch in Google Scholar

Zhu J, Zhang D, Liu X, Yu G, Cai X, Xu C, et al. Zebrafish prmt5 arginine methyltransferase is essential for germ cell development. Development. 2019; 146:dev179572. doi: 10.1242/dev.179572 ZhuJ ZhangD LiuX YuG CaiX XuC Zebrafish prmt5 arginine methyltransferase is essential for germ cell development Development 2019 146 dev179572. 10.1242/dev.179572 31533925 Otwórz DOISearch in Google Scholar

Radion E, Morgunova V, Ryazansky S, Akulenko N, Lavrov S, Abramov Y, et al. Key role of piRNAs in telomeric chromatin maintenance and telomere nuclear positioning in Drosophila germline. Epigenetics Chromatin. 2018; 11:40. doi: 10.1186/s13072-018-0210-4 RadionE MorgunovaV RyazanskyS AkulenkoN LavrovS AbramovY Key role of piRNAs in telomeric chromatin maintenance and telomere nuclear positioning in Drosophila germline Epigenetics Chromatin 2018 11 40 10.1186/s13072-018-0210-4 604398430001204 Otwórz DOISearch in Google Scholar

Li Z, You L, Yan D, James AA, Huang Y, Tan A. Bombyx mori histone methyltransferase BmAsh2 is essential for silkworm piRNA-mediated sex determination. PLoS Genet. 2018; 14:e1007245. doi: 10.1371/journal.pgen.1007245 LiZ YouL YanD JamesAA HuangY TanA Bombyx mori histone methyltransferase BmAsh2 is essential for silkworm piRNA-mediated sex determination PLoS Genet 2018 14 e1007245 10.1371/journal.pgen.1007245 584182629474354 Otwórz DOISearch in Google Scholar

Robine N, Lau NC, Balla S, Jin Z, Okamura K, Kuramochi-Miyagawa S, et al. A broadly conserved pathway generates 3′UTR-directed primary piRNAs. Curr Biol. 2009; 19:2066–76. RobineN LauNC BallaS JinZ OkamuraK Kuramochi-MiyagawaS A broadly conserved pathway generates 3′UTR-directed primary piRNAs Curr Biol 2009 19 2066 76 10.1016/j.cub.2009.11.064281247820022248 Search in Google Scholar

Rouget C, Papin C, Boureux A, Meunier A-C, Franco B, Robine N, et al. Maternal mRNA deadenylation and decay by the piRNA pathway in the early Drosophila embryo. Nature. 2010; 467(7319):1128–32. RougetC PapinC BoureuxA MeunierA-C FrancoB RobineN Maternal mRNA deadenylation and decay by the piRNA pathway in the early Drosophila embryo Nature 2010 467 7319 1128 32 10.1038/nature09465450574820953170 Search in Google Scholar

Dai P, Wang X, Gou L-T, Li Z-T, Wen Z, Chen Z-G, et al. A translation-activating function of MIWI/piRNA during mouse spermiogenesis. Cell. 2019; 179:1566–81.e16. doi: 10.1016/j.cell.2019.11.022 DaiP WangX GouL-T LiZ-T WenZ ChenZ-G A translation-activating function of MIWI/piRNA during mouse spermiogenesis Cell 2019 179 1566 81.e16 10.1016/j.cell.2019.11.022 813932331835033 Otwórz DOISearch in Google Scholar

Mani SR, Megosh H, Lin H. PIWI proteins are essential for early Drosophila embryogenesis. Dev Biol. 2014; 385:340–9. ManiSR MegoshH LinH PIWI proteins are essential for early Drosophila embryogenesis Dev Biol 2014 385 340 9 10.1016/j.ydbio.2013.10.017391587924184635 Search in Google Scholar

Bahn JH, Zhang Q, Li F, Chan T-M, Lin X, Kim Y, et al. The landscape of microRNA, Piwi-interacting RNA, and circular RNA in human saliva. Clin Chem. 2015; 61:221–30. BahnJH ZhangQ LiF ChanT-M LinX KimY The landscape of microRNA, Piwi-interacting RNA, and circular RNA in human saliva Clin Chem 2015 61 221 30 10.1373/clinchem.2014.230433433288525376581 Search in Google Scholar

Lenart P, Novak J, Bienertova-Vasku J. PIWI-piRNA pathway: setting the pace of aging by reducing DNA damage. Mech Ageing Dev. 2018; 173:29–38. LenartP NovakJ Bienertova-VaskuJ PIWI-piRNA pathway: setting the pace of aging by reducing DNA damage Mech Ageing Dev 2018 173 29 38 10.1016/j.mad.2018.03.00929580825 Search in Google Scholar

Rajasethupathy P, Antonov I, Sheridan R, Frey S, Sander C, Tuschl T, Kandel ER. A role for neuronal piRNAs in the epigenetic control of memory-related synaptic plasticity. Cell. 2012; 149:693–707. RajasethupathyP AntonovI SheridanR FreyS SanderC TuschlT KandelER A role for neuronal piRNAs in the epigenetic control of memory-related synaptic plasticity Cell 2012 149 693 707 10.1016/j.cell.2012.02.057344236622541438 Search in Google Scholar

Kolliopoulou A, Santos D, Taning CNT, Wynant N, Vanden Broeck J, Smagghe G, Swevers L. PIWI pathway against viruses in insects. Wiley Interdiscip Rev RNA. 2019; 10:e1555. doi: 10.1002/wrna.1555 KolliopoulouA SantosD TaningCNT WynantN Vanden BroeckJ SmaggheG SweversL PIWI pathway against viruses in insects Wiley Interdiscip Rev RNA 2019 10 e1555 10.1002/wrna.1555 31183996 Otwórz DOISearch in Google Scholar

Henaoui IS, Jacovetti C, Mollet IG, Guay C, Sobel J, Eliasson L, Regazzi R. PIWI-interacting RNAs as novel regulators of pancreatic beta cell function. Diabetologia. 2017; 60:1977–86. HenaouiIS JacovettiC MolletIG GuayC SobelJ EliassonL RegazziR PIWI-interacting RNAs as novel regulators of pancreatic beta cell function Diabetologia 2017 60 1977 86 10.1007/s00125-017-4368-228711973 Search in Google Scholar

Zhou S, Yang S, Li F, Hou J, Chang H. P-element Induced WImpy protein-like RNA-mediated gene silencing 2 regulates tumor cell progression, apoptosis, and metastasis in oral squamous cell carcinoma. J Int Med Res. 2021; 49:3000605211053158. doi: 10.1177/03000605211053158 ZhouS YangS LiF HouJ ChangH P-element Induced WImpy protein-like RNA-mediated gene silencing 2 regulates tumor cell progression, apoptosis, and metastasis in oral squamous cell carcinoma J Int Med Res 2021 49 3000605211053158. 10.1177/03000605211053158 857351834738477 Otwórz DOISearch in Google Scholar

Xie K, Zhang K, Kong J, Wang C, Gu Y, Liang C, et al. Cancer-testis gene PIWIL1 promotes cell proliferation, migration, and invasion in lung adenocarcinoma. Cancer Med. 2018; 7:157–66. XieK ZhangK KongJ WangC GuY LiangC Cancer-testis gene PIWIL1 promotes cell proliferation, migration, and invasion in lung adenocarcinoma Cancer Med 2018 7 157 66 10.1002/cam4.1248577400229168346 Search in Google Scholar

Yao J, Wang YW, Fang BB, Zhang SJ, Cheng BL. piR-651 and its function in 95-D lung cancer cells. Biomed Rep. 2016; 4:546–50. YaoJ WangYW FangBB ZhangSJ ChengBL piR-651 and its function in 95-D lung cancer cells Biomed Rep 2016 4 546 50 10.3892/br.2016.628484078327123245 Search in Google Scholar

Zhang S-J, Yao J, Shen B-Z, Li G-B, Kong S-S, Bi D-D, et al. Role of piwi-interacting RNA-651 in the carcinogenesis of non-small cell lung cancer. Oncol Lett. 2018; 15:940–6. ZhangS-J YaoJ ShenB-Z LiG-B KongS-S BiD-D Role of piwi-interacting RNA-651 in the carcinogenesis of non-small cell lung cancer Oncol Lett 2018 15 940 6 10.3892/ol.2017.7406577278829399156 Search in Google Scholar

Li D, Luo Y, Gao Y, Yang Y, Wang Y, Xu Y, et al. piR-651 promotes tumor formation in non-small cell lung carcinoma through the upregulation of cyclin D1 and CDK4. Int J Mol Med. 2016; 38:927–36. LiD LuoY GaoY YangY WangY XuY piR-651 promotes tumor formation in non-small cell lung carcinoma through the upregulation of cyclin D1 and CDK4 Int J Mol Med 2016 38 927 36 10.3892/ijmm.2016.267127431575 Search in Google Scholar

Reeves ME, Firek M, Jliedi A, Amaar YG. Identification and characterization of RASSF1C piRNA target genes in lung cancer cells. Oncotarget. 2017; 8:34268–82. ReevesME FirekM JliediA AmaarYG Identification and characterization of RASSF1C piRNA target genes in lung cancer cells Oncotarget 2017 8 34268 82 10.18632/oncotarget.15965547096628423657 Search in Google Scholar

Chen S, Ben S, Xin J, Li S, Zheng R, Wang H, et al. The biogenesis and biological function of PIWI-interacting RNA in cancer. J Hematol Oncol. 2021; 14:93. doi: 10.1186/s13045-021-01104-3 ChenS BenS XinJ LiS ZhengR WangH The biogenesis and biological function of PIWI-interacting RNA in cancer J Hematol Oncol 2021 14 93 10.1186/s13045-021-01104-3 819980834118972 Otwórz DOISearch in Google Scholar

Rui, Y. piRNAs variants and lung cancer risk: a post-GWAS study [Masters Public Health thesis]. New Haven (CI): Yale Univ; 2016. Available from: https://elischolar.library.yale.edu/ysphtdl/1335 RuiY. piRNAs variants and lung cancer risk: a post-GWAS study [Masters Public Health thesis] New Haven (CI) Yale Univ 2016 Available from: https://elischolar.library.yale.edu/ysphtdl/1335 Search in Google Scholar

Liang D, Dong M, Hu L-J, Fang Z-H, Xu X, Shi E-H, Yang Y-J. Hiwi knockdown inhibits the growth of lung cancer in nude mice. Asian Pac J Cancer Prev. 2013; 14:1067–72. LiangD DongM HuL-J FangZ-H XuX ShiE-H YangY-J Hiwi knockdown inhibits the growth of lung cancer in nude mice Asian Pac J Cancer Prev 2013 14 1067 72 10.7314/APJCP.2013.14.2.106723621188 Search in Google Scholar

Reeves ME, Firek M, Chen ST, Amaar YG. Evidence that RASSF1C stimulation of lung cancer cell proliferation depends on IGFBP-5 and PIWIL1 expression levels. PloS One. 2014; 9:e101679. doi: 10.1371/journal.pone.0101679 ReevesME FirekM ChenST AmaarYG Evidence that RASSF1C stimulation of lung cancer cell proliferation depends on IGFBP-5 and PIWIL1 expression levels PloS One 2014 9 e101679 10.1371/journal.pone.0101679 409014825007054 Otwórz DOISearch in Google Scholar

Wang Y, Gable T, Ma MZ, Clark D, Zhao J, Zhang Y, et al. A piRNA-like small RNA induces chemoresistance to cisplatin-based therapy by inhibiting apoptosis in lung squamous cell carcinoma. Mol Ther Nucleic Acids. 2017; 6:269–78. WangY GableT MaMZ ClarkD ZhaoJ ZhangY A piRNA-like small RNA induces chemoresistance to cisplatin-based therapy by inhibiting apoptosis in lung squamous cell carcinoma Mol Ther Nucleic Acids 2017 6 269 78 10.1016/j.omtn.2017.01.003536350928325293 Search in Google Scholar

Brock M, Mei Y. Protein functional effector sncRNAs (pfeRNAs) in lung cancer. Cancer Lett. 2017; 403:138–43. BrockM MeiY Protein functional effector sncRNAs (pfeRNAs) in lung cancer Cancer Lett 2017 403 138 43 10.1016/j.canlet.2017.06.01328642173 Search in Google Scholar

Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011; 144:646–74. HanahanD WeinbergRA Hallmarks of cancer: the next generation Cell 2011 144 646 74 10.1016/j.cell.2011.02.01321376230 Search in Google Scholar

Polecane artykuły z Trend MD

Zaplanuj zdalną konferencję ze Sciendo