Critical appraisal of the piRNA-PIWI axis in cancer and cancer stem cells
Status PubMed-not-MEDLINE Language English Country England, Great Britain Media electronic
Document type Journal Article, Review
Grant support
NV19-03-00501
Ministry of Health of the Czech Republic
NV19-03-00501
Ministry of Health of the Czech Republic
NV19-03-00501
Ministry of Health of the Czech Republic
NV19-03-00501
Ministry of Health of the Czech Republic
LX22NPO5102
European Union
LX22NPO5102
European Union
LX22NPO5102
European Union
PubMed
38303021
PubMed Central
PMC10836005
DOI
10.1186/s40364-024-00563-3
PII: 10.1186/s40364-024-00563-3
Knihovny.cz E-resources
- Keywords
- Cancer, Cancer stem cells, PIWI proteins, PIWI-interacting RNAs, piRNAs,
- Publication type
- Journal Article MeSH
- Review MeSH
Small noncoding RNAs play an important role in various disease states, including cancer. PIWI proteins, a subfamily of Argonaute proteins, and PIWI-interacting RNAs (piRNAs) were originally described as germline-specific molecules that inhibit the deleterious activity of transposable elements. However, several studies have suggested a role for the piRNA-PIWI axis in somatic cells, including somatic stem cells. Dysregulated expression of piRNAs and PIWI proteins in human tumors implies that, analogously to their roles in undifferentiated cells under physiological conditions, these molecules may be important for cancer stem cells and thus contribute to cancer progression. We provide an overview of piRNA biogenesis and critically review the evidence for the role of piRNA-PIWI axis in cancer stem cells. In addition, we examine the potential of piRNAs and PIWI proteins to become biomarkers in cancer.
Department of Biochemistry Faculty of Science Masaryk University Brno Czech Republic
Department of Biology Faculty of Medicine Masaryk University Brno Czech Republic
Department of Comprehensive Cancer Care Masaryk Memorial Cancer Institute Brno Czech Republic
Department of Pathology University Hospital Brno Brno Czech Republic
See more in PubMed
Wang X, Ramat A, Simonelig M, Liu MF. Emerging roles and functional mechanisms of PIWI-interacting RNAs. Nat Rev Mol Cell Biol. 2023;24(2):123–141. doi: 10.1038/s41580-022-00528-0. PubMed DOI
Aravin AA, Naumova NM, Tulin AV, Vagin VV, Rozovsky YM, Gvozdev VA. Double-stranded RNA-mediated silencing of genomic tandem repeats and transposable elements in the D. melanogaster germline. Curr Biol. 2001;11(13):1017–27. doi: 10.1016/S0960-9822(01)00299-8. PubMed DOI
Ozata DM, Gainetdinov I, Zoch A, O’Carroll D, Zamore PD. PIWI-interacting RNAs: small RNAs with big functions. Nat Rev Genet. 2019;20(2):89–108. doi: 10.1038/s41576-018-0073-3. PubMed DOI
Grimson A, Srivastava M, Fahey B, Woodcroft BJ, Rosaria HC, King N, et al. The early origins of microRNAs and Piwi-interacting RNAs in animals. Nature. 2009;292(3):342–351. PubMed PMC
Batista PJ, Ruby JG, Claycomb JM, Chiang R, Fahlgren N, Kasschau KD, et al. PRG-1 and 21U-RNAs interact to form the piRNA complex required for fertility in C. elegans. Mol Cell. 2008;31(1):67–78. doi: 10.1016/j.molcel.2008.06.002. PubMed DOI PMC
Suzuki R, Honda S, Kirino Y. PIWI expression and function in cancer. Front Genet. 2012;3(OCT):1–8. PubMed PMC
Jia DD, Jiang H, Zhang YF, Zhang Y, Qian LL, Zhang YF. The regulatory function of piRNA/PIWI complex in cancer and other human diseases: the role of DNA methylation. Int J Biol Sci. 2022;18(8):3358–3373. doi: 10.7150/ijbs.68221. PubMed DOI PMC
Iwasaki YW, Siomi MC, Siomi H. PIWI-interacting RNA: Its biogenesis and functions. Annu Rev Biochem. 2015;84:405–433. doi: 10.1146/annurev-biochem-060614-034258. PubMed DOI
Lewis SH, Quarles KA, Yang Y, Tanguy M, Frézal L, Smith SA, et al. Pan-arthropod analysis reveals somatic piRNAs as an ancestral defence against transposable elements. Nat Ecol Evol. 2018;2(1):174–181. doi: 10.1038/s41559-017-0403-4. PubMed DOI PMC
Jehn J, Gebert D, Pipilescu F, Stern S, Kiefer JST, Hewel C, et al. PIWI genes and piRNAs are ubiquitously expressed in mollusks and show patterns of lineage-specific adaptation. Commun Biol. 2018;1(1):137. doi: 10.1038/s42003-018-0141-4. PubMed DOI PMC
Qiao D, Zeeman AM, 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(25):3988–3999. doi: 10.1038/sj.onc.1205505. PubMed DOI
Lee JH, Jung C, Javadian-Elyaderani P, Schweyer S, Schütte D, Shoukier M, et al. Pathways of proliferation and antiapoptosis driven in breast cancer stem cells by stem cell protein Piwil2. Cancer Res. 2010;70(11):4569–4579. doi: 10.1158/0008-5472.CAN-09-2670. PubMed DOI
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(1):157–166. doi: 10.1002/cam4.1248. PubMed DOI PMC
Nikpour P, Forouzandeh-Moghaddam M, Ziaee SAM, Dokun OY, Schulz WA, Mowla SJ. Absence of PIWIL2 (HILI) expression in human bladder cancer cell lines and tissues. Cancer Epidemiol. 2009;33(3–4):271–275. doi: 10.1016/j.canep.2009.06.011. PubMed DOI
Sasaki T, Shiohama A, Minoshima S, Shimizu N. Identification of eight members of the argonaute family in the human genome. Genomics. 2003;82(3):323–330. doi: 10.1016/S0888-7543(03)00129-0. PubMed DOI
Unhavaithaya Y, Hao Y, Beyret E, Yin H, Kuramochi-Miyagawa S, Nakano T, et al. MILI, a PIWI-interacting RNA-binding protein, is required for germ line stem cell self-renewal and appears to positively regulate translation. J Biol Chem. 2009;284(10):6507–6519. doi: 10.1074/jbc.M809104200. PubMed DOI PMC
Sun YH, Xie LH, Zhuo X, Chen Q, Ghoneim D, Zhang B, et al. Domestic chickens activate a piRNA defense against avian leukosis virus. eLife. 2017;6:1–24. doi: 10.7554/eLife.24695. PubMed DOI PMC
Malone CD, Brennecke J, Dus M, Stark A, McCombie WR, Sachidanandam R, et al. Specialized piRNA pathways act in germline and somatic tissues of the drosophila ovary. Cell. 2009;137(3):522–535. doi: 10.1016/j.cell.2009.03.040. PubMed DOI PMC
Vagin VV, Sigova A, Li C, Seitz H, Gvozdev V, Zamore PD. A distinct small RNA pathway silences selfish genetic elements in the germline. Science. 2006;313(5785):320–324. doi: 10.1126/science.1129333. PubMed DOI
Brennecke J, Aravin AA, Stark A, Dus M, Kellis M, Sachidanandam R, et al. Discrete small RNA-generating loci as master regulators of transposon activity in drosophila. Cell. 2007;128(6):1089–1103. doi: 10.1016/j.cell.2007.01.043. PubMed DOI
Gan H, Lin X, Zhang Z, Zhang W, Liao S, Wang L, et al. piRNA profiling during specific stages of mouse spermatogenesis. RNA. 2011;17(7):1191–1203. doi: 10.1261/rna.2648411. PubMed DOI PMC
Klattenhoff C, Xi H, Li C, Lee S, Xu J, Khurana JS, et al. The drosophila HP1 homolog rhino is required for transposon silencing and piRNA production by dual-strand clusters. Cell. 2009;138(6):1137–1149. doi: 10.1016/j.cell.2009.07.014. PubMed DOI PMC
Mohn F, Sienski G, Handler D, Brennecke J. The rhino-deadlock-cutoff complex licenses noncanonical transcription of dual-strand piRNA clusters in drosophila. Cell. 2014;157(6):1364–1379. doi: 10.1016/j.cell.2014.04.031. PubMed DOI
Andersen PR, Tirian L, Vunjak M, Brennecke J. A heterochromatin-dependent transcription machinery drives piRNA expression. Nature. 2017;549(7670):54–59. doi: 10.1038/nature23482. PubMed DOI PMC
Zhang Z, Wang J, Schultz N, Zhang F, Parhad SS, Tu S, et al. The HP1 homolog rhino anchors a nuclear complex that suppresses piRNA precursor splicing. Cell. 2014;157(6):1353–1363. doi: 10.1016/j.cell.2014.04.030. PubMed DOI PMC
Czech B, Hannon GJ. One loop to rule them all: the ping-pong cycle and piRNA-guided silencing. Trends Biochem Sci. 2016;41(4):324–337. doi: 10.1016/j.tibs.2015.12.008. PubMed DOI PMC
Chang TH, Mattei E, Gainetdinov I, Colpan C, Weng Z, Zamore PD. Maelstrom represses canonical polymerase II transcription within Bi-directional piRNA clusters in drosophila melanogaster. Mol Cell. 2019;73(2):291–303.e6. doi: 10.1016/j.molcel.2018.10.038. PubMed DOI PMC
Li XZ, Roy CK, Dong X, Bolcun-Filas E, Wang J, Han BW, et al. An ancient transcription factor initiates the burst of piRNA production during early meiosis in mouse testes. Mol Cell. 2013;50(1):67–81. doi: 10.1016/j.molcel.2013.02.016. PubMed DOI PMC
Zhang F, Wang J, Xu J, Zhang Z, Koppetsch BS, Schultz N, et al. UAP56 couples piRNA clusters to the perinuclear transposon silencing machinery. Cell. 2012;151(4):871–884. doi: 10.1016/j.cell.2012.09.040. PubMed DOI PMC
Yu T, Fan K, Özata DM, Zhang G, Fu Y, Theurkauf WE, et al. Long first exons and epigenetic marks distinguish conserved pachytene piRNA clusters from other mammalian genes. Nat Commun. 2021;12(1):73. doi: 10.1038/s41467-020-20345-3. PubMed DOI PMC
Czech B, Munafò M, Ciabrelli F, Eastwood EL, Fabry MH, Kneuss E, et al. PiRNA-guided genome defense: from biogenesis to silencing. Annu Rev Genet. 2018;52:131–157. doi: 10.1146/annurev-genet-120417-031441. PubMed DOI PMC
Ipsaro JJ, Haase AD, Knott SR, Joshua-Tor L, Hannon GJ. The structural biochemistry of Zucchini implicates it as a nuclease in piRNA biogenesis. Nature. 2012;491(7423):279–283. doi: 10.1038/nature11502. PubMed DOI PMC
Saito K, Sakaguchi Y, Suzuki T, Suzuki T, Siomi H, Siomi MC. Pimet, the drosophila homolog of HEN1, mediates 2′- O -methylation of Piwi- interacting RNAs at their 3′ ends. Genes Dev. 2007;21(13):1603–1608. doi: 10.1101/gad.1563607. PubMed DOI PMC
Huang X, Fejes Tóth K, Aravin AA. piRNA biogenesis in drosophila melanogaster. Trends Genet. 2017;33(11):882–894. doi: 10.1016/j.tig.2017.09.002. PubMed DOI PMC
Gainetdinov I, Colpan C, Arif A, Cecchini K, Zamore PD. A Single mechanism of biogenesis, initiated and directed by PIWI proteins, explains piRNA production in most animals. Mol Cell. 2018;71(5):775–790.e5. doi: 10.1016/j.molcel.2018.08.007. PubMed DOI PMC
Zhang Y, Guo R, Cui Y, Zhu Z, Zhang Y, Wu H, et al. An essential role for PNLDC1 in piRNA 3′ end trimming and male fertility in mice. Cell Res. 2017;27(11):1392–1396. doi: 10.1038/cr.2017.125. PubMed DOI PMC
Pastore B, Hertz HL, Price IF, Tang W. pre-piRNA trimming and 2′-O-methylation protect piRNAs from 3′ tailing and degradation in C. elegans. Cell Rep. 2021;36(9):109640. doi: 10.1016/j.celrep.2021.109640. PubMed DOI PMC
Bamezai S, Rawat VPS, Buske C. Concise review: The Piwi-piRNA Axis: pivotal beyond transposon silencing. Stem Cells. 2012;30(12):2603–2611. doi: 10.1002/stem.1237. PubMed DOI
Watanabe T, Cheng EC, Zhong M, Lin H. Retrotransposons and pseudogenes regulate mRNAs and lncRNAs via the piRNA pathway in the germline. Genome Res. 2015;25(3):368–380. doi: 10.1101/gr.180802.114. PubMed DOI PMC
Kim IV, Duncan EM, Ross EJ, Gorbovytska V, Nowotarski SH, Elliott SA, et al. Planarians recruit piRNAs for mRNA turnover in adult stem cells. Genes Dev. 2019;33(21–22):1575–1590. doi: 10.1101/gad.322776.118. PubMed DOI PMC
Aravin AA, Sachidanandam R, Bourc’his D, Schaefer C, Pezic D, Toth KF, et al. A piRNA pathway primed by individual transposons is linked to de novo DNA methylation in mice. Mol Cell. 2008;31(6):785–99. doi: 10.1016/j.molcel.2008.09.003. PubMed DOI PMC
Yu Y, Gu J, Jin Y, Luo Y, Preall JB, Ma J, et al. Panoramix enforces piRNA-dependent cotranscriptional silencing. Science. 2015;350(6258):339–342. doi: 10.1126/science.aab0700. PubMed DOI PMC
Iwasaki YW, Sriswasdi S, Kinugasa Y, Adachi J, Horikoshi Y, Shibuya A, et al. Piwi–piRNA complexes induce stepwise changes in nuclear architecture at target loci. EMBO J. 2021;40(18):1–19. doi: 10.15252/embj.2021108345. PubMed DOI PMC
Sienski G, Dönertas D, Brennecke J. Transcriptional silencing of transposons by Piwi and maelstrom and its impact on chromatin state and gene expression. Cell. 2012;151(5):964–980. doi: 10.1016/j.cell.2012.10.040. PubMed DOI PMC
Pezic D, Manakov SA, Sachidanandam R, Aravin AA. piRNA pathway targets active LINE1 elements to establish the repressive H3K9me3 mark in germ cells. Genes Dev. 2014;28(13):1410–1428. doi: 10.1101/gad.240895.114. PubMed DOI PMC
Wu D, Fu H, Zhou H, Su J, Zhang F, Shen J. Effects of novel ncRNA molecules, p15-piRNAs, on the methylation of DNA and histone H3 of the CDKN2B promoter region in U937 cells. J Cell Biochem. 2015;116(12):2744–2754. doi: 10.1002/jcb.25199. PubMed DOI
He X, Chen X, Zhang X, Duan X, Pan T, Hu Q, et al. An Lnc RNA (GAS5)/SnoRNA-derived piRNA induces activation of TRAIL gene by site-specifically recruiting MLL/COMPASS-like complexes. Nucleic Acids Res. 2015;43(7):3712–3725. doi: 10.1093/nar/gkv214. PubMed DOI PMC
Kuramochi-Miyagawa S, Watanabe T, Gotoh K, Totoki Y, Toyoda A, Ikawa M, et al. DNA methylation of retrotransposon genes is regulated by Piwi family members MILI and MIWI2 in murine fetal testes. Genes Dev. 2008;22(7):908–917. doi: 10.1101/gad.1640708. PubMed DOI PMC
Aravin AA, Sachidanandam R, Girard A, Fejes-Toth K, Hannon GJ. Developmentally regulated piRNA clusters implicate MILI in transposon control. Science. 2007;316(5825):744–747. doi: 10.1126/science.1142612. PubMed DOI
Peng JC, Lin H. Beyond transposons: The epigenetic and somatic functions of the Piwi-piRNA mechanism. Curr Opin Cell Biol. 2013;25(2):190–194. doi: 10.1016/j.ceb.2013.01.010. PubMed DOI PMC
Zoch A, Auchynnikava T, Berrens RV, Kabayama Y, Schöpp T, Heep M, et al. SPOCD1 is an essential executor of piRNA-directed de novo DNA methylation. Nature. 2020;584(7822):635–639. doi: 10.1038/s41586-020-2557-5. PubMed DOI PMC
Kojima-Kita K, Kuramochi-Miyagawa S, Nakayama M, Miyata H, Jacobsen SE, Ikawa M, et al. MORC3, a novel MIWI2 association partner, as an epigenetic regulator of piRNA dependent transposon silencing in male germ cells. Sci Rep. 2021;11(1):20472. doi: 10.1038/s41598-021-98940-7. PubMed DOI PMC
Rojas-Rıós P, Simonelig M. piRNAs and PIWI proteins: Regulators of gene expression in development and stem cells. Dev Camb. 2018;145(17):dev161786. PubMed
Rusell S. Transposons and the PIWI pathway: genome defense in gametes and embryos. Lecture. 2018;156(4):R111–24. PubMed
Yan H, Wu QL, Sun CY, Ai LS, 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(1):196–206. doi: 10.1038/leu.2014.135. PubMed DOI
Anzelon TA, Chowdhury S, Hughes SM, Xiao Y, Lander GC, MacRae IJ. Structural basis for piRNA targeting. Nature. 2021;597(7875):285–289. doi: 10.1038/s41586-021-03856-x. PubMed DOI PMC
Shen EZ, Chen H, Ozturk AR, Tu S, Shirayama M, Tang W, et al. Identification of piRNA binding sites reveals the argonaute regulatory landscape of the C. elegans germline. Cell. 2018;172(5):937–951.e18. doi: 10.1016/j.cell.2018.02.002. PubMed DOI PMC
Gainetdinov I, Vega-Badillo J, Cecchini K, Bagci A, Colpan C, De D, et al. Relaxed targeting rules help PIWI proteins silence transposons. Nature. 2023;619(7969):394–402. doi: 10.1038/s41586-023-06257-4. PubMed DOI PMC
Ramat A, Simonelig M. Functions of PIWI proteins in gene regulation: new arrows added to the piRNA quiver. Trends Genet. 2021;37(2):188–200. doi: 10.1016/j.tig.2020.08.011. PubMed DOI
Barckmann B, Pierson S, Dufourt J, Papin C, Armenise C, Port F, et al. Aubergine iCLIP reveals piRNA-dependent decay of mRNAs involved in germ cell development in the early embryo. Cell Rep. 2015;12(7):1205–1216. doi: 10.1016/j.celrep.2015.07.030. PubMed DOI PMC
Rouget C, Papin C, Boureux A, Meunier AC, Franco B, Robine N, et al. Maternal mRNA deadenylation and decay by the piRNA pathway in the early drosophila embryo. Nature. 2010;467(7319):1128–1132. doi: 10.1038/nature09465. PubMed DOI PMC
Gou LT, Dai P, Yang JH, Xue Y, Hu YP, Zhou Y, et al. Pachytene piRNAs instruct massive mRNA elimination during late spermiogenesis. Cell Res. 2014;24(6):680–700. doi: 10.1038/cr.2014.41. PubMed DOI PMC
Choi H, Wang Z, Dean J. Sperm acrosome overgrowth and infertility in mice lacking chromosome 18 pachytene piRNA. Cohen PE, editor. PLOS Genet. 2021;17(4):e1009485. doi: 10.1371/journal.pgen.1009485. PubMed DOI PMC
Wu PH, Fu Y, Cecchini K, Özata DM, Arif A, Yu T, et al. The evolutionarily conserved piRNA-producing locus pi6 is required for male mouse fertility. Nat Genet. 2020;52(7):728–739. doi: 10.1038/s41588-020-0657-7. PubMed DOI PMC
Peng L, Song L, Liu C, Lv X, Li X, Jie J, et al. piR-55490 inhibits the growth of lung carcinoma by suppressing mTOR signaling. Tumor Biol. 2016;37(2):2749–2756. doi: 10.1007/s13277-015-4056-0. PubMed DOI
Grivna ST, Pyhtila B, Lin H. MIWI associates with translational machinery and PIWI-interacting RNAs (piRNAs) in regulating spermatogenesis. Proc Natl Acad Sci. 2006;103(36):13415–13420. doi: 10.1073/pnas.0605506103. PubMed DOI PMC
Dai P, Wang X, Gou LT, Li ZT, Wen Z, Chen ZG, et al. A Translation-Activating Function of MIWI/piRNA during Mouse Spermiogenesis. Cell. 2019;179(7):1566–1581.e16. doi: 10.1016/j.cell.2019.11.022. PubMed DOI PMC
Ramat A, Garcia-Silva MR, Jahan C, Naït-Saïdi R, Dufourt J, Garret C, et al. The PIWI protein aubergine recruits eIF3 to activate translation in the germ plasm. Cell Res. 2020;30(5):421–435. doi: 10.1038/s41422-020-0294-9. PubMed DOI PMC
Dufourt J, Bontonou G, Chartier A, Jahan C, Meunier AC, Pierson S, et al. PiRNAs and Aubergine cooperate with Wispy poly(A) polymerase to stabilize mRNAs in the germ plasm. Nat Commun. 2017;8(1):1–12. doi: 10.1038/s41467-017-01431-5. PubMed DOI PMC
Gou LT, Kang JY, Dai P, Wang X, Li F, Zhao S, et al. Ubiquitination-deficient mutations in human piwi cause male infertility by impairing histone-to-protamine exchange during spermiogenesis. Cell. 2018;169(6):1090–104. doi: 10.1016/j.cell.2017.04.034. PubMed DOI PMC
Genzor P, Cordts SC, Bokil NV, Haase AD. Aberrant expression of select piRNA-pathway genes does not reactivate piRNA silencing in cancer cells. Proc Natl Acad Sci. 2019;116(23):11111–11112. doi: 10.1073/pnas.1904498116. PubMed DOI PMC
Li F, Yuan P, Rao M, Jin CH, Tang W, Rong YF, et al. piRNA-independent function of PIWIL1 as a co-activator for anaphase promoting complex/cyclosome to drive pancreatic cancer metastasis. Nat Cell Biol. 2020;22(4):425–438. doi: 10.1038/s41556-020-0486-z. PubMed DOI
Mai D, Ding P, Tan L, Zhang J, Pan Z, Bai R, et al. PIWI-interacting RNA-54265 is oncogenic and a potential therapeutic target in colorectal adenocarcinoma. Theranostics. 2018;8(19):5213–5230. doi: 10.7150/thno.28001. PubMed DOI PMC
Shi S, Yang ZZ, Liu S, Yang F, Lin H. PIWIL1 promotes gastric cancer via a piRNA-independent mechanism. Proc Natl Acad Sci U S A. 2020;117(36):22390–22401. doi: 10.1073/pnas.2008724117. PubMed DOI PMC
Clara JA, Monge C, Yang Y, Takebe N. Targeting signalling pathways and the immune microenvironment of cancer stem cells — a clinical update. Nat Rev Clin Oncol. 2020;17(4):204–232. doi: 10.1038/s41571-019-0293-2. PubMed DOI
Walcher L, Kistenmacher AK, Suo H, Kitte R, Dluczek S, Strauß A, et al. Cancer stem cells—origins and biomarkers: perspectives for targeted personalized therapies. Front Immunol. 2020;7(11):1280. doi: 10.3389/fimmu.2020.01280. PubMed DOI PMC
Toh TB, Lim JJ, Chow EKH. Epigenetics in cancer stem cells. Mol Cancer. 2017;16(1):29. doi: 10.1186/s12943-017-0596-9. PubMed DOI PMC
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(4):217–223. doi: 10.1016/j.suronc.2013.07.001. PubMed DOI
Jin L, Zhang Z, Wang Z, Tan X, Wang Z, Shen L, et al. Novel piRNA MW557525 regulates the growth of Piwil2-iCSCs and maintains their stem cell pluripotency. Mol Biol Rep. 2022;49(7):6957–6969. doi: 10.1007/s11033-022-07443-9. PubMed DOI
Ding X, Li Y, Lü J, Zhao Q, Guo Y, Lu Z, et al. piRNA-823 Is involved in cancer stem cell regulation through altering DNA methylation in association with luminal breast cancer. Front Cell Dev Biol. 2021;9(March):1–10. PubMed PMC
Zhao Q, Qian L, Guo Y, Lü J, Li D, Xie H, et al. IL11 signaling mediates piR-2158 suppression of cell stemness and angiogenesis in breast cancer. Theranostics. 2023;13(7):2337–2349. doi: 10.7150/thno.82538. PubMed DOI PMC
Navarro A, Tejero R, Viñolas N, Cordeiro A, Marrades RM, Fuster D, et al. The significance of PIWI family expression in human lung embryogenesis and non-small cell lung cancer. Oncotarget. 2015;6(31):31544–56. PubMed PMC
Litwin M, Dubis J, Arczyñska K, Piotrowska A, Frydlewicz A, Karczewski M, et al. Correlation of HIWI and HILI expression with cancer stem cell markers in colorectal cancer. Anticancer Res. 2015;35(6):3317–3324. PubMed
Huang H, Yu X, Han X, Hao J, Zhao J, Bebek G, et al. Piwil1 regulates glioma stem cell maintenance and glioblastoma progression. Cell Rep. 2021;34(1):108522. doi: 10.1016/j.celrep.2020.108522. PubMed DOI PMC
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(5):1853–1860. doi: 10.3892/or.2014.3401. PubMed DOI
Chen Z, Che Q, He X, Wang F, Wang H, Zhu M, et al. Stem cell protein Piwil1 endowed endometrial cancer cells with stem-like properties via inducing epithelial-mesenchymal transition. BMC Cancer. 2015;15(1):1–13. doi: 10.1186/s12885-015-1794-8. PubMed DOI PMC
Wang Y, Yao L, Teng Y, Yin H, Wu Q. PIWIL1 drives chemoresistance in multiple myeloma by modulating mitophagy and the myeloma stem cell population. Front Oncol. 2022;10:11. PubMed PMC
Wang SS, Jiang J, Liang XH, Tang YL. Links between cancer stem cells and epithelial – mesenchymal transition. OncoTargets Ther. 2015;8:2973–80. PubMed PMC
Smith AG, Macleod KF. Autophagy, cancer stem cells and drug resistance. J Pathol. 2019;247(5):708–718. doi: 10.1002/path.5222. PubMed DOI PMC
Feng D, Peng C, Li C, Zhou Y, Li M, Ling B, et al. Identification and characterization of cancer stem-like cells from primary carcinoma of the cervix uteri. Oncol Rep. 2010;23(3):861–867. PubMed
Chen L, Shen R, Ye Y, Pu XA, Liu X, Duan W, et al. Precancerous stem cells have the potential for both benign and malignant differentiation. PLoS ONE. 2007;2(3):e293. doi: 10.1371/journal.pone.0000293. PubMed DOI PMC
Shahali M, Kabirsalmani M, Nayernia K, Reza H, Soleimanpoulichaei HR, Vasei M, et al. A novel in vitro model for cancer stem cell culture using ectopically expressed Piwil2 stable cell line. Cell. 2013;15(3):250–7. PubMed PMC
Zhang D, Wu X, Liu X, Cai C, Zeng G, Rohozinski J, et al. Piwil2-transfected human fibroblasts are cancer stem cell-like and genetically unstable. Oncotarget. 2017;8(7):12259–12271. doi: 10.18632/oncotarget.14696. PubMed DOI PMC
Feng D, Yan K, Zhou Y, Liang H, Liang J, Zhao W, et al. Piwil2 is reactivated by HPV oncoproteins and initiates cell reprogramming via epigenetic regulation during cervical cancer tumorigenesis. Oncotarget. 2016;7(40):64575–64588. doi: 10.18632/oncotarget.11810. PubMed DOI PMC
Smith BA, Balanis NG, Nanjundiah A, Sheu KM, Tsai BL, Zhang Q, et al. A human adult stem cell signature marks aggressive variants across epithelial cancers. Cell Rep. 2018;24(12):3353–3366.e5. doi: 10.1016/j.celrep.2018.08.062. PubMed DOI PMC
Law PTY, Qin H, Ching AKK, Lai KP, Co NN, He M, et al. Deep sequencing of small RNA transcriptome reveals novel non-coding RNAs in hepatocellular carcinoma. J Hepatol. 2013;58(6):1165–1173. doi: 10.1016/j.jhep.2013.01.032. PubMed DOI
Zhang L, Meng X, Li D, Han X. piR-001773 and piR-017184 promote prostate cancer progression by interacting with PCDH9. Cell Signal. 2020;76:109780. doi: 10.1016/j.cellsig.2020.109780. PubMed DOI
Wu YJ, Wang J, Zhang P, Yuan LX, Ju LL, Wang HX, et al. PIWIL1 interacting RNA piR-017724 inhibits proliferation, invasion, and migration, and inhibits the development of HCC by silencing PLIN3. Front Oncol. 2023;11(13):1203821. doi: 10.3389/fonc.2023.1203821. PubMed DOI PMC
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(10):1094–1102. doi: 10.1093/carcin/bgv105. PubMed DOI PMC
Liu Q, Chen Q, Zhou Z, Tian Z, Zheng X, Wang K. piRNA-18 Inhibition Cell Proliferation, Migration and Invasion in Colorectal Cancer. Biochem Genet. 2023;61(5):1881–97. PubMed
Liu T, Wang J, Sun L, Li M, He X, Jiang J, et al. Piwi-interacting RNA-651 promotes cell proliferation and migration and inhibits apoptosis in breast cancer by facilitating DNMT1-mediated PTEN promoter methylation. Cell Cycle Georget Tex. 2021;20(16):1603–1616. doi: 10.1080/15384101.2021.1956090. PubMed DOI PMC
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(3):927–936. doi: 10.3892/ijmm.2016.2671. PubMed DOI
Cordeiro A, Navarro A, Gaya A, Díaz-Beyá M, Gonzalez-Farré B, Castellano JJ, et al. PiwiRNA-651 as marker of treatment response and survival in classical Hodgkin lymphoma. Oncotarget. 2016;7(29):46002–46013. doi: 10.18632/oncotarget.10015. PubMed DOI PMC
Yin J, Jiang X, Qi W, Ji C, Xie X, Zhang D, et al. piR-823 contributes to colorectal tumorigenesis by enhancing the transcriptional activity of HSF 1. Cancer Sci. 2017;108(9):1746–1756. doi: 10.1111/cas.13300. PubMed DOI PMC
Sabbah NA, Abdalla WM, Mawla WA, AbdAlMonem N, Gharib AF, Abdul-Saboor A, et al. piRNA-823 Is a unique potential diagnostic non-invasive biomarker in colorectal cancer patients. Genes. 2021;12(4):598. doi: 10.3390/genes12040598. PubMed DOI PMC
Cheng J, Deng H, Xiao B, Zhou H, Zhou F, Shen Z, et al. 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(1):12–17. doi: 10.1016/j.canlet.2011.10.004. PubMed DOI
Su JF, Zhao F, Gao ZW, Hou YJ, Li YY, Duan LJ, et al. piR-823 demonstrates tumor oncogenic activity in esophageal squamous cell carcinoma through DNA methylation induction via DNA methyltransferase 3B. Pathol - Res Pract. 2020;216(4):152848. doi: 10.1016/j.prp.2020.152848. PubMed DOI
Iliev R, Fedorko M, Machackova T, Mlcochova H, Svoboda M, Pacik D, et al. Expression levels of PIWI-interacting RNA, piR-823, are deregulated in tumor tissue, blood serum and urine of patients with renal cell carcinoma. Anticancer Res. 2016;36(12):6419–6424. doi: 10.21873/anticanres.11239. PubMed DOI
Weng W, Liu N, Toiyama Y, Kusunoki M, Nagasaka T, Fujiwara T, et al. Novel evidence for a PIWI-interacting RNA (piRNA) as an oncogenic mediator of disease progression, and a potential prognostic biomarker in colorectal cancer. Mol Cancer. 2018;17(1):16. doi: 10.1186/s12943-018-0767-3. PubMed DOI PMC
Zhang W, Zheng Z, Wang K, Mao W, Li X, Wang G, et al. piRNA-1742 promotes renal cell carcinoma malignancy by regulating USP8 stability through binding to hnRNPU and thereby inhibiting MUC12 ubiquitination. Exp Mol Med. 2023;55(6):1258–1271. doi: 10.1038/s12276-023-01010-3. PubMed DOI PMC
Huang G, Hu H, Xue X, Shen S, Gao E, Guo G, et al. Altered expression of piRNAs and their relation with clinicopathologic features of breast cancer. Clin Transl Oncol. 2013;15(7):563–568. doi: 10.1007/s12094-012-0966-0. PubMed DOI
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(102):37616–37626. doi: 10.18632/oncotarget.26331. PubMed DOI PMC
Bartos M, Siegl F, Kopkova A, Radova L, Oppelt J, Vecera M, et al. Small RNA sequencing Identifies PIWI-Interacting RNAs deregulated in glioblastoma—piR-9491 and piR-12488 reduce tumor cell colonies in vitro. Front Oncol. 2021;13(11):707017. doi: 10.3389/fonc.2021.707017. PubMed DOI PMC
Chang Z, Ji G, Huang R, Chen H, Gao Y, Wang W, et al. PIWI-interacting RNAs piR-13643 and piR-21238 are promising diagnostic biomarkers of papillary thyroid carcinoma. Aging. 2020;12(10):9292–9310. doi: 10.18632/aging.103206. PubMed DOI PMC
Xie Q, Li Z, Luo X, Wang D, Zhou Y, Zhao J, et al. piRNA-14633 promotes cervical cancer cell malignancy in a METTL14-dependent m6A RNA methylation manner. J Transl Med. 2022;20(1):51. doi: 10.1186/s12967-022-03257-2. PubMed DOI PMC
Yin J, Qi W, Ji C, Zhang D, Xie X, Ding Q, et al. Small RNA sequencing revealed aberrant piRNA expression profiles in colorectal cancer. Oncol Rep. 2019;42(1):263–72. PubMed
Li G, Yi X, Du S, Gong L, Wu Q, Cai J, et al. Tumour-derived exosomal piR-25783 promotes omental metastasis of ovarian carcinoma by inducing the fibroblast to myofibroblast transition. Oncogene. 2023;42(6):421–33. PubMed
Liu X, Zheng J, Xue Y, Yu H, Gong W, Wang P, et al. PIWIL3/OIP5-AS1/miR-367-3p/CEBPA feedback loop regulates the biological behavior of glioma cells. Theranostics. 2018;8(4):1084–1105. doi: 10.7150/thno.21740. PubMed DOI PMC
Han H, Fan G, Song S, Jiang Y, Qian C, Zhang W, et al. piRNA-30473 contributes to tumorigenesis and poor prognosis by regulating m6A RNA methylation in DLBCL. Blood. 2021;137(12):1603–1614. doi: 10.1182/blood.2019003764. PubMed DOI
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(1):61. doi: 10.1186/s13046-015-0180-3. PubMed DOI PMC
Du X, Li H, Xie X, Shi L, Wu F, Li G, et al. piRNA-31115 promotes cell proliferation and invasion via PI3K/AKT pathway in clear cell renal carcinoma. Dis Markers. 2021;2021:6915329. doi: 10.1155/2021/6915329. PubMed DOI PMC
Zhang L, Meng X, Pan C, Qu F, Gan W, Xiang Z, et al. piR-31470 epigenetically suppresses the expression of glutathione S-transferase pi 1 in prostate cancer via DNA methylation. Cell Signal. 2020;67:109501. doi: 10.1016/j.cellsig.2019.109501. PubMed DOI
Zhao C, Tolkach Y, Schmidt D, Toma M, Muders MH, Kristiansen G, et al. Mitochondrial PIWI-interacting RNAs are novel biomarkers for clear cell renal cell carcinoma. World J Urol. 2019;37(8):1639–1647. doi: 10.1007/s00345-018-2575-1. PubMed DOI
Reeves ME, Firek M, Jliedi A, Amaar YG. Identification and characterization of RASSF1C piRNA target genes in lung cancer cells. Oncotarget. 2017;8(21):34268–34282. doi: 10.18632/oncotarget.15965. PubMed DOI PMC
Wang Q, Chen P, Wang X, Wu Y, Xia K, Mu X, et al. piR-36249 and DHX36 together inhibit testicular cancer cells progression by upregulating OAS2. Non-Coding RNA Res. 2023;8(2):174–186. doi: 10.1016/j.ncrna.2022.12.004. PubMed DOI PMC
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(1):9. doi: 10.1186/s12943-019-0940-3. PubMed DOI PMC
Ding L, Wang R, Xu W, Shen D, Cheng S, Wang H, et al. PIWI-interacting RNA 57125 restrains clear cell renal cell carcinoma metastasis by downregulating CCL3 expression. Cell Death Discov. 2021;7(1):333. doi: 10.1038/s41420-021-00725-4. PubMed DOI PMC
Li Y, Dong Y, Zhao S, Gao J, Hao X, Wang Z, et al. Serum-derived piR-hsa-164586 of extracellular vesicles as a novel biomarker for early diagnosis of non-small cell lung cancer. Front Oncol. 2022;28(12):850363. doi: 10.3389/fonc.2022.850363. PubMed DOI PMC
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;23(11):651915. doi: 10.3389/fonc.2021.651915. PubMed DOI PMC
Qu A, Wang W, Yang Y, Zhang X, Dong Y, Zheng G, et al. A serum piRNA signature as promising non-invasive diagnostic and prognostic biomarkers for colorectal cancer. Cancer Manag Res. 2019;11:3703–3720. doi: 10.2147/CMAR.S193266. PubMed DOI PMC
Peng Q, Chiu PKF, Wong CYP, Cheng CKL, Teoh JYC, Ng CF. Identification of piRNA targets in urinary extracellular vesicles for the diagnosis of prostate cancer. Diagnostics. 2021;11(10):1828. doi: 10.3390/diagnostics11101828. PubMed DOI PMC
Ma H, Wang H, Tian F, Zhong Y, Liu Z, Liao A. PIWI-interacting RNA-004800 is regulated by s1p receptor signaling pathway to keep myeloma cell survival. Front Oncol. 2020;15(10):438. doi: 10.3389/fonc.2020.00438. PubMed DOI PMC
Ge L, Zhang N, Li D, Wu Y, Wang H, Wang J. Circulating exosomal small RNAs are promising non-invasive diagnostic biomarkers for gastric cancer. J Cell Mol Med. 2020;24(24):14502–14513. doi: 10.1111/jcmm.16077. PubMed DOI PMC
Wang Z, Yang H, Ma D, Mu Y, Tan X, Hao Q, et al. Serum PIWI-Interacting RNAs piR-020619 and piR-020450 are promising novel biomarkers for early detection of colorectal cancer. Cancer Epidemiol Biomarkers Prev. 2020;29(5):990–998. doi: 10.1158/1055-9965.EPI-19-1148. PubMed DOI
Wang H, Shi B, Zhang X, Shen P, He Q, Yin M, et al. Exosomal hsa-piR1089 promotes proliferation and migration in neuroblastoma via targeting KEAP1. Pathol - Res Pract. 2023;241:154240. doi: 10.1016/j.prp.2022.154240. PubMed DOI
Li W, Gonzalez-Gonzalez M, Sanz-Criado L, Garcia-Carbonero N, Celdran A, Villarejo-Campos P, et al. A novel PiRNA enhances CA19-9 sensitivity for pancreatic cancer identification by liquid biopsy. J Clin Med. 2022;11(24):7310. doi: 10.3390/jcm11247310. PubMed DOI PMC
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(9):1019–1028. doi: 10.1158/1055-9965.EPI-18-0318. PubMed DOI
Mai D, Zheng Y, Guo H, Ding P, Bai R, Li M, et al. Serum piRNA-54265 is a new biomarker for early detection and clinical surveillance of human colorectal cancer. Theranostics. 2020;10(19):8468–8478. doi: 10.7150/thno.46241. PubMed DOI PMC
Ai L, Mu S, Sun C, Fan F, Yan H, Qin Y, et al. Myeloid-derived suppressor cells endow stem-like qualities to multiple myeloma cells by inducing piRNA-823 expression and DNMT3B activation. Mol Cancer. 2019;18(1):88. doi: 10.1186/s12943-019-1011-5. PubMed DOI PMC
Wang S, Jiang X, Xie X, Yin J, Zhang J, Liu T, et al. piR-823 inhibits cell apoptosis via modulating mitophagy by binding to PINK1 in colorectal cancer. Cell Death Dis. 2022;13(5):465. doi: 10.1038/s41419-022-04922-6. PubMed DOI PMC
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(5):546–550. doi: 10.3892/br.2016.628. PubMed DOI PMC
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(3):2286–2299. doi: 10.1002/jcp.29136. PubMed DOI
Das B, Jain N, Mallick B. piR-39980 promotes cell proliferation, migration and invasion, and inhibits apoptosis via repression of SERPINB1 in human osteosarcoma. Biol Cell. 2020;112(3):73–91. doi: 10.1111/boc.201900063. PubMed DOI
Das B, Roy J, Jain N, Mallick B. Tumor suppressive activity of PIWI-interacting RNA in human fibrosarcoma mediated through repression of RRM2. Mol Carcinog. 2019;58(3):344–357. doi: 10.1002/mc.22932. PubMed DOI
Das B, Jain N, Mallick B. piR-39980 mediates doxorubicin resistance in fibrosarcoma by regulating drug accumulation and DNA repair. Commun Biol. 2021;4(1):1312. doi: 10.1038/s42003-021-02844-1. PubMed DOI PMC
Sharma AK, Nelson MC, Brandt JE, Wessman M, Mahmud N, Weller KP, et al. Human cells express the hiwi gene, a human homologue of the Drosophila gene piwi. Blood J American Soc Hematol. 2001;97(2):426–34. PubMed
Liu C, Qu L, Dong B, Xing X, Ren T, Zeng Y, et al. Combined phenotype of 4 markers improves prognostic value of patients with colon cancer. Am J Med Sci. 2012;343(4):295–302. doi: 10.1097/MAJ.0b013e31822cb4cd. PubMed DOI
Raeisossadati R, Abbaszadegan MR, Moghbeli M, Tavassoli A, Kihara AH, Forghanifard MM. Aberrant expression of DPPA2 and HIWI genes in colorectal cancer and their impacts on poor prognosis. Tumor Biol. 2014;35(6):5299–5305. doi: 10.1007/s13277-014-1690-x. PubMed DOI
Sun R, Gao CL, Li DH, Li BJ, Ding YH. Expression status of PIWIL1 as a prognostic marker of colorectal cancer. Dis Markers. 2017;2017:1204937. doi: 10.1155/2017/1204937. PubMed DOI PMC
Yang L, Bi L, Liu Q, Zhao M, Cao B, Li D, et al. Hiwi promotes the proliferation of colorectal cancer cells via upregulating global DNA methylation. Dis Markers. 2015;2015:383056. doi: 10.1155/2015/383056. PubMed DOI PMC
Sun G, Wang Y, Sun L, Luo H, Liu N, Fu Z, et al. Clinical significance of Hiwi gene expression in gliomas. Brain Res. 2011;1373:183–188. doi: 10.1016/j.brainres.2010.11.097. PubMed DOI
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(8):1922–1929. doi: 10.1002/ijc.21575. PubMed DOI
Wang Y, Liu Y, Shen X, Zhang X, Chen X, Yang C, et al. The PIWI protein acts as a predictive marker for human gastric cancer. Int J Clin Exp Pathol. 2012;5(4):315–325. PubMed PMC
Ferreira HJ, Heyn H, Garcia del Muro X, Vidal A, Larriba S, Muñoz C, et al. Epigenetic loss of the machinery in human testicular tumorigenesis. Epigenetics. 2014;9(1):113–8. doi: 10.4161/epi.27237. PubMed DOI PMC
Wang DW, Wang ZH, Wang LL, Song Y, Zhang GZ. Overexpression of Hiwi promotes growth of human breast cancer cells. Asian Pac J Cancer Prev. 2014;15(18):7553–7558. doi: 10.7314/APJCP.2014.15.18.7553. PubMed DOI
Cao J, Xu G, Lan J, Huang Q, Tang Z, Tian L. High expression of piwi-like RNA-mediated gene silencing 1 is associated with poor prognosis via regulating transforming growth factor-β receptors and cyclin-dependent kinases in breast cancer. Mol Med Rep. 2016;13(3):2829–2835. doi: 10.3892/mmr.2016.4842. PubMed DOI
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(20):10646–10658. doi: 10.1074/jbc.M116.723239. PubMed DOI PMC
Wang Y, Liu J, Wu G, Yang F. Manipulations in HIWI level exerts influence on the proliferation of human non-small cell lung cancer cells. Exp Ther Med. 2016;11(5):1971–1976. doi: 10.3892/etm.2016.3106. PubMed DOI PMC
Qu X, Liu J, Zhong X, Li X, Zhang Q. PIWIL2 promotes progression of non-small cell lung cancer by inducing CDK2 and Cyclin A expression. J Transl Med. 2015;13(1):1–10. doi: 10.1186/s12967-015-0666-y. PubMed DOI PMC
Jiang J, Zhang H, Tang Q, Hao B, Shi R. Expression of HIWI in human hepatocellular carcinoma. Cell Biochem Biophys. 2011;61(1):53–58. doi: 10.1007/s12013-011-9160-1. PubMed DOI
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. 2015;11(2):1455–1461. doi: 10.3892/mmr.2014.2847. PubMed DOI
Zhao YM, Zhou JM, Wang LR, He HW, Wang XL, Tao ZH, et al. HIWI is associated with prognosis in patients with hepatocellular carcinoma after curative resection. Cancer. 2012;118(10):2708–2717. doi: 10.1002/cncr.26524. PubMed DOI
Stöhr CG, Steffens S, Polifka I, Jung R, Kahlmeyer A, Ivanyi P, et al. Piwi-like 1 protein expression is a prognostic factor for renal cell carcinoma patients. Sci Rep. 2019;9(1):1741. doi: 10.1038/s41598-018-38254-3. PubMed DOI PMC
Iliev R, Stanik M, Fedorko M, Poprach A, Vychytilova-Faltejskova P, Slaba K, et al. Decreased expression levels of PIWIL1, PIWIL2, and PIWIL4 are associated with worse survival in renal cell carcinoma patients. OncoTargets Ther. 2016;9:217–222. PubMed PMC
Li D, Sun X, Yan D, Huang J, Luo Q, Tang H, et al. Piwil2 modulates the proliferation and metastasis of colon cancer via regulation of matrix metallopeptidase 9 transcriptional activity. Exp Biol Med. 2012;237(10):1231–1240. doi: 10.1258/ebm.2012.011380. PubMed DOI
Oh SJ, Kim SM, Kim YO, Chang HK. Clinicopathologic implications of PIWIL2 expression in colorectal cancer. Korean J Pathol. 2012;46(4):318–323. doi: 10.4132/KoreanJPathol.2012.46.4.318. PubMed DOI PMC
Li J, Xu L, Bao Z, Xu P, Chang H, Wu J, et al. High expression of PIWIL2 promotes tumor cell proliferation, migration and predicts a poor prognosis in glioma. Oncol Rep. 2017;38(1):183–192. doi: 10.3892/or.2017.5647. PubMed DOI
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(3):1735–1740. doi: 10.3892/ol.2015.3392. PubMed DOI PMC
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(4):328–337. PubMed PMC
Greither T, Koser F, Kappler M, Bache M, Lautenschläger C, Göbel S, et al. Expression of human Piwi-like genes is associated with prognosis for soft tissue sarcoma patients. BMC Cancer. 2012;12:1–8. doi: 10.1186/1471-2407-12-272. PubMed DOI PMC
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(2):156–169. PubMed PMC
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. Hum Mol Genet. 2006;15(2):201–211. doi: 10.1093/hmg/ddi430. PubMed DOI
Pammer J, Rossiter H, Bilban M, Eckhart L, Buchberger M, Monschein L, et al. PIWIL-2 and piRNAs are regularly expressed in epithelia of the skin and their expression is related to differentiation. Arch Dermatol Res. 2020;312(10):705–714. doi: 10.1007/s00403-020-02052-7. PubMed DOI PMC
Jiang L, Wang WJ, Li ZW, Wang XZ. Downregulation of Piwil3 suppresses cell proliferation, migration and invasion in gastric cancer. Cancer Biomark. 2017;20(4):499–509. doi: 10.3233/CBM-170324. PubMed DOI
Su C, Ren ZJ, Wang F, Liu M, Li X, Tang H. PIWIL4 regulates cervical cancer cell line growth and is involved in down-regulating the expression of p14ARF and p53. FEBS Lett. 2012;586(9):1356–1362. doi: 10.1016/j.febslet.2012.03.053. PubMed DOI
Hempfling AL, Lim SL, Adelson DL, Evans J, O’Connor AE, Qu ZP, et al. Expression patterns of HENMT1 and PIWIL1 in human testis: implications for transposon expression. Reproduction. 2017;154(4):363–374. doi: 10.1530/REP-16-0586. PubMed DOI
Virant-Klun I, Leicht S, Hughes C, Krijgsveld J. Identification of maturation-specific proteins by single-cell proteomics of human oocytes. Mol Cell Proteomics. 2016;15(8):2616–2627. doi: 10.1074/mcp.M115.056887. PubMed DOI PMC
Lim SL, Ricciardelli C, Oehler MK, De Arao Tan IMD, Russell D, Grützner F. Overexpression of piRNA pathway genes in epithelial ovarian cancer. PLoS ONE. 2014;9(6):1–11. doi: 10.1371/journal.pone.0099687. PubMed DOI PMC
Li W, Martinez-Useros J, Garcia-Carbonero N, Fernandez-Aceñero MJ, Orta A, Ortega-Medina L, et al. The clinical significance of PIWIL3 and PIWIL4 expression in pancreatic cancer. J Clin Med. 2020;9(5):1252. doi: 10.3390/jcm9051252. PubMed DOI PMC
Tan M, Van Tol HTA, Rosenkranz D, Roovers EF, Damen MJ, Stout TAE, et al. PIWIL3 forms a complex with TDRKH in Mammalian Oocytes. Cells. 2020;9(6):1356. doi: 10.3390/cells9061356. PubMed DOI PMC
Sohni A, Tan K, Song HW, Burow D, de Rooij DG, Laurent L, et al. The neonatal and adult human testis defined at the single-cell level. Cell Rep. 2019;26(6):1501–1517.e4. doi: 10.1016/j.celrep.2019.01.045. PubMed DOI PMC
Sugimoto K, Kage H, Aki N, Sano A, Kitagawa H, Nagase T, et al. The induction of H3K9 methylation by PIWIL4 at the p16Ink4a locus. Biochem Biophys Res Commun. 2007;359(3):497–502. doi: 10.1016/j.bbrc.2007.05.136. PubMed DOI
Bordeaux J, Welsh AW, Agarwal S, Killiam E, Baquero MT, Hanna JA, et al. Antibody validation. Biotechniques. 2010;48(3):197–209. doi: 10.2144/000113382. PubMed DOI PMC
Balaratnam S, West N, Basu S. A piRNA utilizes HILI and HIWI2 mediated pathway to down-regulate ferritin heavy chain 1 mRNA in human somatic cells. Nucleic Acids Res. 2018;46(20):10635–48. PubMed PMC
Tosar JP, Rovira C, Cayota A. Non-coding RNA fragments account for the majority of annotated piRNAs expressed in somatic non-gonadal tissues. Commun Biol. 2018;1(1):2. doi: 10.1038/s42003-017-0001-7. PubMed DOI PMC
Yang Q, Li R, Lyu Q, Hou L, Liu Z, Sun Q, et al. Single-cell CAS-seq reveals a class of short PIWI-interacting RNAs in human oocytes. Nat Commun. 2019;10(1):3389. doi: 10.1038/s41467-019-11312-8. PubMed DOI PMC