1,890
Views
3
CrossRef citations to date
0
Altmetric
Review

PIWI interacting RNAs perspectives: a new avenues in future cancer investigations

ORCID Icon, , , , , , & show all
Pages 10401-10419 | Received 28 Aug 2021, Accepted 19 Oct 2021, Published online: 09 Dec 2021

References

  • Amaral PP, Dinger ME, Mercer TR, et al. The eukaryotic genome as an RNA machine. science. 2008;319(5871):1787–1789.
  • Cui D-Y, Wang -J-J, He S-M. The research advance of the piRNA function. Sheng li ke xue jin zhan [Progress in physiology]. 2016;47(3):182–186.
  • Zhu X, Jiang S, Wu Z, et al. Long non-coding RNA TTN antisense RNA 1 facilitates hepatocellular carcinoma progression via regulating miR-139-5p/SPOCK1 axis. Bioengineered. 2021;12(1):578–588.
  • Iyer MK, Niknafs YS, Malik R, et al. The landscape of long noncoding RNAs in the human transcriptome. Nat Genet. 2015;47(3):199–208.
  • Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. cell. 2005;120(1):15–20.
  • Shi Z, Shen C, Yu C, et al. Long non-coding RNA LINC00997 silencing inhibits the progression and metastasis of colorectal cancer by sponging miR-512-3p. Bioengineered. 2021;12(1):627–639.
  • Meseure D, Alsibai KD. Part 1: The PIWI-piRNA pathway is an immune-like surveillance process that controls genome integrity by silencing transposable elements. In: Colin Logie and Tobias Aurelius Knoch (eds) Chromatin and Epigenetics. IntechOpen; 2018:233-251. London, UK:  IntechOpen.
  • Knauss JL, Sun T. Regulatory mechanisms of long noncoding RNAs in vertebrate central nervous system development and function. Neuroscience. 2013;235:200–214.
  • Zhang Y-P, Cheng Y-B, Li S, et al. An epithelial-mesenchymal transition-related long non-coding RNA signature to predict overall survival and immune microenvironment in kidney renal clear cell carcinoma. Bioengineered. 2021;12(1):555–564.
  • Zhao C, Tolkach Y, Schmidt D, et al. Mitochondrial PIWI-interacting RNAs are novel biomarkers for clear cell renal cell carcinoma. World J Urol. 2019;37(8):1639–1647.
  • Farazi TA, Juranek SA, Tuschl T (2008a). The growing catalog of small RNAs and their association with distinct Argonaute/Piwi family members.
  • Hamilton AJ, Baulcombe Dc. A species of small antisense RNA in posttranscriptional gene silencing in plants. science. 1999;286(5441):950–952.
  • Leung YY, Kuksa PP, Amlie-Wolf A, et al. DASHR: database of small human noncoding RNAs. Nucleic Acids Res. 2016;44(D1)(D1):D216–D222.
  • Chalbatani GM, Dana H, Memari F, et al. Biological function and molecular mechanism of piRNA in cancer. Pract Lab Med. 2019;13:e00113.
  • Iwasaki YW, Siomi MC, Siomi H. PIWI-interacting RNA: its biogenesis and functions. Annu Rev Biochem. 2015;84(1):405–433.
  • Kang J, Huang X, Dong W, et al. MicroRNA-1269b inhibits gastric cancer development through regulating methyltransferase-like 3 (METTL3). Bioengineered. 2021;12(1):1150–1160.
  • Ng KW, Anderson C, Marshall EA, et al. Piwi-interacting RNAs in cancer: emerging functions and clinical utility. Mol Cancer. 2016;15(1):1–13.
  • Nozawa M, Kinjo S (2016). Noncoding RNAs, origin and evolution of.
  • 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.
  • Rayford KJ, Cooley A, Rumph JT, et al. piRNAs as modulators of disease pathogenesis. Int J Mol Sci. 2021;22(5):2373.
  • Wang L, Ge S, Zhou F. MicroRNA-487a-3p inhibits the growth and invasiveness of oral squamous cell carcinoma by targeting PPM1A. Bioengineered. 2021;12(1):937–947.
  • Xu J, Yang X, Zhou Q, et al. Biological significance of piRNA in liver cancer: a review. Biomarkers. 2020;25(6):436–440.
  • Höck J, Weinmann L, Ender C, et al. Proteomic and functional analysis of Argonaute‐containing mRNA–protein complexes in human cells. EMBO Rep. 2007;8(11):1052–1060.
  • Fitzmaurice C, Dicker D, Pain A, et al. The global burden of cancer 2013. JAMA Oncol. 2015;1(4):505–527.
  • Ashktorab H, Brim H. Blood-based liquid biopsies: a noninvasive and cost-effective tool for improved risk assessment and identification of lymph node metastasis in patients with submucosal T1 colorectal cancer. Gastroenterology. 2021;161(1):29–31.
  • Aziz N, Hong YH, Jo M, et al. Molecular signatures of JMJD10/MINA53 in gastric cancer. Cancers (Basel). 2020;12(5):5.
  • Brim H, Ashktorab H. Integrating microbiomics in cancer management. Nat Rev Cancer. 2021;21(11):684–685.
  • Deng S, Zhang X, Qin Y, et al. miRNA‐192 and‐215 activate Wnt/β‐catenin signaling pathway in gastric cancer via APC. J Cell Physiol. 2020;235(9):6218–6229.
  • Erfani M, Hosseini SV, Mokhtari M, et al. Altered ARID1A expression in colorectal cancer. BMC Cancer. 2020;20(1):1–13.
  • Igder S, Mohammadiasl J, Azadpour S, et al. KRAS mutation and abnormal expression of Cripto‐1 as two potential candidate biomarkers for detection of colorectal cancer development. J Cell Biochem. 2020;121(4):2901–2908.
  • Zhang X, Peng Y, Yuan Y, et al. Histone methyltransferase SET8 is regulated by miR-192/215 and induces oncogene-induced senescence via p53-dependent DNA damage in human gastric carcinoma cells. Cell Death Dis. 2020;11(10):937.
  • Igder S, Mohammadiasl J, Mokarram P. Altered miR-21, miRNA-148a expression in relation to KRAS mutation status as indicator of adenoma-carcinoma transitional pattern in colorectal adenoma and carcinoma lesions. Biochem Genet. 2019;57(6):767–780.
  • Poursheikhani A, Bahmanpour Z, Razmara E, et al. Non-coding RNAs underlying chemoresistance in gastric cancer. Cell Oncol. 2020;43:961–988.
  • Aravin AA, Lagos-Quintana M, Yalcin A, et al. The small RNA profile during Drosophila melanogaster development. Dev Cell. 2003;5(2):337–350.
  • Aravin AA, Naumova NM, Tulin AV, et al. Double-stranded RNA-mediated silencing of genomic tandem repeats and transposable elements in the D. melanogaster germline. Curr Biol. 2001;11(13):1017–1027.
  • Vagin VV, Sigova A, Li C, et al. A distinct small RNA pathway silences selfish genetic elements in the germline. science. 2006;313(5785):320–324.
  • Aravin A, Gaidatzis D, Pfeffer S, et al. A novel class of small RNAs bind to MILI protein in mouse testes. Nature. 2006;442(7099):203–207.
  • Kim VN. Small RNAs just got bigger: Piwi-interacting RNAs (piRNAs) in mammalian testes. Genes Dev. 2006;20(15):1993–1997.
  • Williams Z, Morozov P, Mihailovic A, et al. Discovery and characterization of piRNAs in the human fetal ovary. Cell Rep. 2015;13(4):854–863.
  • Farazi TA, Juranek SA, Tuschl T. The growing catalog of small RNAs and their association with distinct Argonaute/Piwi family members. Development. 2008b;135(7):1201–1214.
  • Weng W, Li H, Goel A. Piwi-interacting RNAs (piRNAs) and cancer: emerging biological concepts and potential clinical implications. Biochim Biophys Acta (BBA)- Rev Cancer. 2019;1871(1):160–169.
  • Kirino Y, Mourelatos Z. Mouse Piwi-interacting RNAs are 2′-O-methylated at their 3′ termini. Nat Struct Mol Biol. 2007;14(4):347–348.
  • Saito K, Sakaguchi Y, Suzuki T, et al. 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.
  • Luteijn MJ, Ketting RF. PIWI-interacting RNAs: from generation to transgenerational epigenetics. Nat Rev Genet. 2013;14(8):523–534.
  • Suzuki R, Honda S, Kirino Y. PIWI expression and function in cancer. Front Genet. 2012;3:204.
  • Yamanaka S, Siomi MC, Siomi H. piRNA clusters and open chromatin structure. Mob DNA. 2014;5(1):1–12.
  • Thomson T, Lin H. The biogenesis and function of PIWI proteins and piRNAs: progress and prospect. Annual Review of Cell and Developmental. 2009;25(1):355–376.
  • Weick E-M, Miska EA. piRNAs: from biogenesis to function. Development. 2014;141(18):3458–3471.
  • Keam SP, Young PE, McCorkindale AL, et al. The human Piwi protein Hiwi2 associates with tRNA-derived piRNAs in somatic cells. Nucleic Acids Res. 2014;42(14):8984–8995.
  • Krishnan P, Ghosh S, Wang B, et al. Genome-wide profiling of transfer RNAs and their role as novel prognostic markers for breast cancer. Sci Rep. 2016;6(1):32843.
  • Zhong F, Zhou N, Wu K, et al. A SnoRNA-derived piRNA interacts with human interleukin-4 pre-mRNA and induces its decay in nuclear exosomes. Nucleic Acids Res. 2015;43(21):10474–10491.
  • Aravin AA, Sachidanandam R, Girard A, et al. Developmentally regulated piRNA clusters implicate MILI in transposon control. science. 2007;316(5825):744–747.
  • Batista PJ, Ruby JG, Claycomb JM, 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.
  • Brennecke J, Aravin AA, Stark A, et al. Discrete small RNA-generating loci as master regulators of transposon activity in Drosophila. cell. 2007;128(6):1089–1103.
  • Cox DN, Chao A, Lin H. Piwi encodes a nucleoplasmic factor whose activity modulates the number and division rate of germline stem cells. Development. 2000;127(3):503–514.
  • Deng W, Lin H. Miwi, a murine homolog of piwi, encodes a cytoplasmic protein essential for spermatogenesis. Dev Cell. 2002;2(6):819–830.
  • Schüpbach T, Wieschaus E. Female sterile mutations on the second chromosome of Drosophila melanogaster. II. Mutations blocking oogenesis or altering egg morphology. Genetics. 1991;129(4):1119–1136.
  • Zhao S, Gou L-T, Zhang M, et al. piRNA-triggered MIWI ubiquitination and removal by APC/C in late spermatogenesis. Dev Cell. 2013;24(1):13–25.
  • Malone CD, Hannon GJ. Small RNAs as guardians of the genome. cell. 2009;136(4):656–668.
  • Siomi MC, Sato K, Pezic D, et al. PIWI-interacting small RNAs: the vanguard of genome defence. Nat Rev Mol Cell Biol. 2011;12(4):246–258.
  • Sasaki T, Shiohama A, Minoshima S, et al. Identification of eight members of the Argonaute family in the human genome☆. Genomics. 2003;82(3):323–330.
  • Li C, Vagin VV, Lee S, et al. Without Argonaute3, Aubergine-bound piRNAs collapse but Piwi-bound piRNAs persist. cell. 2009b;137(3):509.
  • Alié A, Leclère L, Jager M, et al. Somatic stem cells express Piwi and Vasa genes in an adult ctenophore: ancient association of “germline genes” with stemness. Dev Biol. 2011;350(1):183–197.
  • Rinkevich Y, Rosner A, Rabinowitz C, et al. Piwi positive cells that line the vasculature epithelium, underlie whole body regeneration in a basal chordate. Dev Biol. 2010;345(1):94–104.
  • Rinkevich Y, Voskoboynik A, Rosner A, et al. Repeated, long-term cycling of putative stem cells between niches in a basal chordate. Dev Cell. 2013;24(1):76–88.
  • Sharma AK, Nelson MC, Brandt JE, et al. Human CD34+ stem cells express the hiwi gene, a human homologue of the Drosophila gene piwi. Blood J Am Soc Hematol. 2001;97(2):426–434.
  • Lee JH, Schütte D, Wulf G, 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.
  • Liu X, Sun Y, Guo J, 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.
  • Miller F, Pozniak C, Walsh G. Neuronal life and death: an essential role for the p53 family. Cell Death Differ. 2000;7(10):880–888.
  • Brower-Toland B, Findley SD, Jiang L, et al. Drosophila PIWI associates with chromatin and interacts directly with HP1a. Genes Dev. 2007;21(18):2300–2311.
  • Li C, Vagin VV, Lee S, et al. Collapse of germline piRNAs in the absence of Argonaute3 reveals somatic piRNAs in flies. cell. 2009a;137(3):509–521.
  • Ross RJ, Weiner MM, Lin H. PIWI proteins and PIWI-interacting RNAs in the soma. Nature. 2014;505(7483):353–359.
  • 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.
  • Henaoui IS, Jacovetti C, Mollet IG, et al. PIWI-interacting RNAs as novel regulators of pancreatic beta cell function. Diabetologia. 2017;60(10):1977–1986.
  • Nandi S, Chandramohan D, Fioriti L, et al. (2016). Roles for small noncoding RNAs in silencing of retrotransposons in the mammalian brain. Proceedings of the National Academy of Sciences,USA, 113( 45), 12697–12702.
  • Bamezai S, Rawat VP, Buske C. Concise review: the Piwi‐piRNA axis: pivotal beyond transposon silencing. Stem Cells. 2012;30(12):2603–2611.
  • Cora E, Pandey RR, Xiol J, et al. The MID-PIWI module of Piwi proteins specifies nucleotide-and strand-biases of piRNAs. Rna. 2014;20(6):773–781.
  • Krishnan P, Damaraju S. The challenges and opportunities in the clinical application of noncoding RNAs: the road map for miRNAs and piRNAs in cancer diagnostics and prognostics. Int J Genomics. 2018;2018:1–18.
  • Cox DN, Chao A, Baker J, et al. A novel class of evolutionarily conserved genes defined by piwi are essential for stem cell self-renewal. Genes Dev. 1998;12(23):3715–3727.
  • Völler D, Linck L, Bruckmann A, et al. Argonaute family protein expression in normal tissue and cancer entities. PLoS One. 2016;11(8):e0161165.
  • Malone CD, Brennecke J, Dus M, et al. Specialized piRNA pathways act in germline and somatic tissues of the Drosophila ovary. cell. 2009;137(3):522–535.
  • Malone CD, Brennecke J, Dus M, et al. Specialized piRNA pathways act in germline and somatic tissues of the Drosophila ovary. cell. 2009;137(3):522–535.
  • Bernstein BE, Meer A, Lander ES. The mammalian epigenome. cell. 2007;128(4):669–681.
  • Han BW, Zamore PD. PiRNAs. Curr Biol. 2014;24(16):R730–R733.
  • Han BW, Wang W, Li C, et al. piRNA-guided transposon cleavage initiates Zucchini-dependent, phased piRNA production. science. 2015;348(6236):817–821.
  • Tsaytler P, Harding HP, Ron D, et al. Selective inhibition of a regulatory subunit of protein phosphatase 1 restores proteostasis. science. 2011;332(6025):91–94.
  • Grimson A, Srivastava M, Fahey B, et al. Early origins and evolution of microRNAs and Piwi-interacting RNAs in animals. Nature. 2008;455(7217):1193–1197.
  • Cheng Y, Wang Q, Jiang W, et al. Emerging roles of piRNAs in cancer: challenges and prospects. Aging (Albany NY). 2019;11(21):9932.
  • Cichocki F, Lenvik T, Sharma N, et al. Cutting edge: KIR antisense transcripts are processed into a 28-base PIWI-like RNA in human NK cells. J Immunol. 2010;185(4):2010–2012.
  • Kazazian HH. Mobile elements: drivers of genome evolution. science. 2004;303(5664):1626–1632.
  • Moyano M, Stefani G. piRNA involvement in genome stability and human cancer. J Hematol Oncol. 2015;8(1):38.
  • Wei JW, Huang K, Yang C, et al. Non-coding RNAs as regulators in epigenetics (Review). Oncol Rep. 2017;37(1):3–9.
  • Yu Y, Xiao J, Hann SS. <p>The emerging roles of PIWI-interacting RNA in human cancers. <![cdata[cancer Management and Research]]>. 2019;11:5895.
  • Mei Y, Wang Y, Kumari P, et al. A piRNA-like small RNA interacts with and modulates p-ERM proteins in human somatic cells. Nat Commun. 2015;6(1):7316.
  • Grivna ST, Pyhtila B, Lin H (2006). MIWI associates with translational machinery and PIWI-interacting RNAs (piRNAs) in regulating spermatogenesis. Proceedings of the National Academy of Sciences, 103( 36), 13415–13420.
  • Unhavaithaya Y, Hao Y, Beyret E, 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.
  • Rojas‐Ríos P, Chartier A, Pierson S, et al. Aubergine and pi RNA s promote germline stem cell self‐renewal by repressing the proto‐oncogene Cbl. EMBO J. 2017;36(21):3194–3211.
  • Ma X, Zhu X, Han Y, et al. Aubergine controls germline stem cell self-renewal and progeny differentiation via distinct mechanisms. Dev Cell. 2017;41(2):157–169. e155.
  • Ashe A, Sapetschnig A, Weick E-M, et al. piRNAs can trigger a multigenerational epigenetic memory in the germline of C. elegans. cell. 2012;150(1):88–99.
  • Pek JW, Kai T. Non-coding RNAs enter mitosis: functions, conservation and implications. Cell Div. 2011;6(1):1–6.
  • Szakmary A, Cox DN, Wang Z, et al. Regulatory relationship among piwi, pumilio, and bag-of-marbles in Drosophila germline stem cell self-renewal and differentiation. Curr Biol. 2005;15(2):171–178.
  • Zhang X, He X, Liu C, et al. IL-4 inhibits the biogenesis of an epigenetically suppressive PIWI-interacting RNA to upregulate CD1a molecules on monocytes/dendritic cells. J Immunol. 2016;196(4):1591–1603.
  • Shirayama M, Seth M, Lee H-C, et al. piRNAs initiate an epigenetic memory of nonself RNA in the C. elegans germline. cell. 2012;150(1):65–77.
  • Stuwe E, Toth KF, Aravin AA. Small but sturdy: small RNAs in cellular memory and epigenetics. Genes Dev. 2014;28(5):423–431.
  • Kawaoka S, Izumi N, Katsuma S, et al. 3′ end formation of PIWI-interacting RNAs in vitro. Mol Cell. 2011;43(6):1015–1022.
  • Khurana JS, Xu J, Weng Z, et al. Distinct functions for the Drosophila piRNA pathway in genome maintenance and telomere protection. PLoS Genet. 2010;6(12):e1001246.
  • Schwager EE, Meng Y, Extavour CG. vasa and piwi are required for mitotic integrity in early embryogenesis in the spider Parasteatoda tepidariorum. Dev Biol. 2015;402(2):276–290.
  • Yin H, Lin H. An epigenetic activation role of Piwi and a Piwi-associated piRNA in Drosophila melanogaster. Nature. 2007;450(7167):304–308.
  • Yin D-T, Wang Q, Chen L, et al. Germline stem cell gene PIWIL2 mediates DNA repair through relaxation of chromatin. PLoS One. 2011;6(11):e27154.
  • Kwon C, Tak H, Rho M, et al. Detection of PIWI and piRNAs in the mitochondria of mammalian cancer cells. Biochem Biophys Res Commun. 2014;446(1):218–223.
  • Fonseca Cabral G, Azevedo Dos Santos Pinheiro J, Vidal AF, et al. piRNAs in gastric cancer: a new approach towards translational research. Int J Mol Sci. 2020;21(6):2126.
  • Bahn JH, Zhang Q, Li F, et al. The landscape of microRNA, Piwi-interacting RNA, and circular RNA in human saliva. Clin Chem. 2015;61(1):221–230.
  • Roy J, Sarkar A, Parida S, et al. Small RNA sequencing revealed dysregulated piRNAs in Alzheimer’s disease and their probable role in pathogenesis. Mol Biosyst. 2017;13(3):565–576.
  • Wang S, Wang Z, Tao R, et al. The potential use of Piwi-interacting RNA biomarkers in forensic body fluid identification: a proof-of-principle study. Forensic Sci Int Genet. 2019;39:129–135.
  • Yang X, Cheng Y, Lu Q, et al. Detection of stably expressed piRNAs in human blood. Int J Clin Exp Med. 2015;8(8):13353.
  • Lee EJ, Banerjee S, Zhou H, et al. Identification of piRNAs in the central nervous system. Rna. 2011;17(6):1090–1099.
  • Rajasethupathy P, Antonov I, Sheridan R, et al. A role for neuronal piRNAs in the epigenetic control of memory-related synaptic plasticity. cell. 2012;149(3):693–707.
  • Roque CG, Hengst U. Wimpy nerves: piRNA pathway curbs axon regrowth after injury. Neuron. 2018;97(3):477–478.
  • Pantano L, Jodar M, Bak M, et al. The small RNA content of human sperm reveals pseudogene-derived piRNAs complementary to protein-coding genes. Rna. 2015;21(6):1085–1095.
  • Zeng Q, Wan H, Zhao S, et al. Role of PIWI‐interacting RNAs on cell survival: proliferation, apoptosis, and cycle. IUBMB Life. 2020;72(9):1870–1878.
  • Meseure D, Alsibai KD. Part 2: Deregulated expressions of PIWI proteins and piRNAs as new candidate biomarkers and potential therapeutic tools in cancer. In: Colin Logie and Tobias Aurelius Knoch (eds)., Chromatin and epigenetics. London, United Kingdom: IntechOpen; 2020:263-274.
  • Siddiqi S, Matushansky I. Piwis and piwi‐interacting RNAs in the epigenetics of cancer. J Cell Biochem. 2012;113(2):373–380.
  • Mei Y, Clark D, Mao L. Novel dimensions of piRNAs in cancer. Cancer Lett. 2013;336(1):46–52.
  • Lim SL, Ricciardelli C, Oehler MK, et al. Overexpression of piRNA pathway genes in epithelial ovarian cancer. PLoS One. 2014;9(6):e99687.
  • Yan H, Wu Q, Sun C, et al. piRNA-823 contributes to tumorigenesis by regulating de novo DNA methylation and angiogenesis in multiple myeloma. Leukemia. 2015;29(1):196–206.
  • Martinez VD, Vucic EA, Thu KL, et al. Unique somatic and malignant expression patterns implicate PIWI-interacting RNAs in cancer-type specific biology. Sci Rep. 2015;5(1):1–17.
  • Tan L, Mai D, Zhang B, et al. PIWI-interacting RNA-36712 restrains breast cancer progression and chemoresistance by interaction with SEPW1 pseudogene SEPW1P RNA. Mol Cancer. 2019;18(1):1–15.
  • Ding X, Li Y, Lü J, 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. DOI:10.3389/fcell.2021.641052
  • Weng W, Liu N, Toiyama Y, 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.
  • Jacobs DI, Qin Q, Lerro MC, et al. PIWI-interacting RNAs in gliomagenesis: evidence from post-GWAS and functional analyses. Cancer Epidemiol Prev Biomarkers. 2016;25(7):1073–1080.
  • Li Y, Wu X, Gao H, et al. Piwi-interacting RNAs (piRNAs) are dysregulated in renal cell carcinoma and associated with tumor metastasis and cancer-specific survival. Mol Med. 2015;21(1):381–388.
  • Chu H, Hui G, Yuan L, et al. Identification of novel piRNAs in bladder cancer. Cancer Lett. 2015;356(2):561–567.
  • Xiao Z, Shen J, Zhang L, et al. Therapeutic targeting of noncoding RNAs in hepatocellular carcinoma: recent progress and future prospects. Oncol Lett. 2018;15(3):3395–3402.
  • Tang X, Xie X, Wang X, et al. The combination of piR-823 and eukaryotic initiation factor 3 B (EIF3B) activates hepatic stellate cells via upregulating TGF-β1 in liver fibrogenesis. Med Sci Monit. 2018;24:9151.
  • Zhang L, Meng X, Li D, et al. piR-001773 and piR-017184 promote prostate cancer progression by interacting with PCDH9. Cell Signal. 2020;76:109780.
  • Qi T, Cao H, Sun H, et al. piR-19166 inhibits migration and metastasis through CTTN/MMPs pathway in prostate carcinoma. Aging (Albany NY). 2020;12(18):18209.
  • Ma H, Wang H, Tian F, et al. PIWI-interacting RNA-004800 is regulated by S1P receptor signaling pathway to keep myeloma cell survival. Front Oncol. 2020;10:438.
  • Baylin SB, Jones PA. A decade of exploring the cancer epigenome—biological and translational implications. Nat Rev Cancer. 2011;11(10):726–734.
  • Tan Y, Liu L, Liao M, et al. Emerging roles for PIWI proteins in cancer. Acta Biochim Biophys Sin (Shanghai). 2015;47(5):315–324.
  • Liu L, Dai Y, Chen J, et al. Maelstrom promotes hepatocellular carcinoma metastasis by inducing epithelial‐mesenchymal transition by way of Akt/GSK‐3β/Snail signaling. Hepatology. 2014;59(2):531–543.
  • Cheng J, Guo J-M, Xiao B-X, et al. piRNA, the new non-coding RNA, is aberrantly expressed in human cancer cells. Clin Chim Acta. 2011;412(17–18):1621–1625.
  • Huang G-L, Hu H, Xue X, et al. Altered expression of piRNAs and their relation with clinicopathologic features of breast cancer. Clin Transl Oncol. 2013;15(7):563–568.
  • Law PT-Y, Qin H, Ching A-K-K, et al. Deep sequencing of small RNA transcriptome reveals novel non-coding RNAs in hepatocellular carcinoma. J Hepatol. 2013;58(6):1165–1173.
  • Asati V, Mahapatra DK, Bharti SK. PI3K/Akt/mTOR and Ras/Raf/MEK/ERK signaling pathways inhibitors as anticancer agents: Structural and pharmacological perspectives. Eur J Med Chem. 2016;109:314–341.
  • Wu X, Pan Y, Fang Y, et al. The biogenesis and functions of piRNAs in human diseases. In Molecular Therapy-Nucleic Acids. 2020a;21:108-120. USA: Elsevier.
  • Jeong H, Park K-H, Lee Y, et al. The regulation and role of piRNAs and PIWI proteins in cancer. Processes. 2021;9(7):1208.
  • Cui L, Lou Y, Zhang X, et al. Detection of circulating tumor cells in peripheral blood from patients with gastric cancer using piRNAs as markers. Clin Biochem. 2011;44(13):1050–1057.
  • Gu X, Wang C, Deng H, et al. Exosomal piRNA profiling revealed unique circulating piRNA signatures of cholangiocarcinoma and gallbladder carcinoma. Acta Biochim Biophys Sin (Shanghai). 2020;52(5):475–484.
  • Iliev R, Fedorko M, Machackova T, 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):6419–6423.
  • Ogawa Y, Taketomi Y, Murakami M, et al. Small RNA transcriptomes of two types of exosomes in human whole saliva determined by next generation sequencing. Biol Pharm Bull. 2013;36(1):66–75.
  • Vychytilova-Faltejskova P, Stitkovcova K, Radova L, et al. Circulating PIWI-interacting RNAs piR-5937 and piR-28876 are promising diagnostic biomarkers of colon cancer. Cancer Epidemiology Biomarkers & Prevention. 2018;27(9):1019–1028.
  • Wang Z, Yang H, Ma D, et al. Serum PIWI-interacting RNAs piR-020619 and piR-020450 are promising novel biomarkers for early detection of colorectal cancer. Cancer Epidemiol Prev Biomarkers. 2020;29(5):990–998.
  • Zhou X, Liu J, Meng A, et al. Gastric juice piR‐1245: a promising prognostic biomarker for gastric cancer. J Clin Lab Anal. 2020;34(4):e23131.
  • Houwing S, Kamminga LM, Berezikov E, et al. A role for Piwi and piRNAs in germ cell maintenance and transposon silencing in Zebrafish. cell. 2007;129(1):69–82.
  • Sarkar A, Ghosh Z. Rejuvenation of piRNAs in emergence of cancer and other diseases. In: Bibekanand Mallick AGO-driven non-coding RNAs. USA: Elsevier; 2019. p. 319–333.
  • Cheng J, Deng H, Xiao B, 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.
  • Zhou H, Guo J-M, Lou Y-R, et al. Detection of circulating tumor cells in peripheral blood from patients with gastric cancer using microRNA as a marker. J Mol Med. 2010;88(7):709–717.
  • Wu X, Pan Y, Fang Y, et al. The biogenesis and functions of piRNAs in human diseases. Mol Ther Nucleic Acids. 2020b;21:108–120.
  • Ren Z, Li Y, Hameed O, et al. Prognostic factors in patients with metastatic breast cancer at the time of diagnosis. Pathol Res Pract. 2014;210(5):301–306.
  • Zhang H, Ren Y, Xu H, et al. The expression of stem cell protein Piwil2 and piR-932 in breast cancer. Surg Oncol. 2013;22(4):217–223.
  • Krishnan P, Ghosh S, Graham K, et al. Piwi-interacting RNAs and PIWI genes as novel prognostic markers for breast cancer. Oncotarget. 2016;7(25):37944.
  • Li D, Luo Y, Gao 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.
  • Yao J, Wang YW, Fang BB, et al. piR-651 and its function in 95-D lung cancer cells. Biomed Rep. 2016;4(5):546–550.
  • Peng L, Song L, Liu C, et al. piR-55490 inhibits the growth of lung carcinoma by suppressing mTOR signaling. Tumor Biol. 2016;37(2):2749–2756.
  • Chu H, Xia L, Qiu X, et al. Genetic variants in noncoding PIWI‐interacting RNA and colorectal cancer risk. Cancer. 2015;121(12):2044–2052.
  • Mai D, Zheng Y, Guo H, et al. Serum piRNA-54265 is a new biomarker for early detection and clinical surveillance of human colorectal cancer. Theranostics. 2020;10(19):8468.
  • Yin J, Jiang XY, Qi W, et al. piR‐823 contributes to colorectal tumorigenesis by enhancing the transcriptional activity of HSF 1. Cancer Sci. 2017;108(9):1746–1756.
  • Yin J, Qi W, Ji CG, et al. Small RNA sequencing revealed aberrant piRNA expression profiles in colorectal cancer. Oncol Rep. 2019;42(1):263–272.
  • Öner Ç, Turgut Coşan D, Çolak E. Estrogen and androgen hormone levels modulate the expression of PIWI interacting RNA in prostate and breast cancer. PLoS One. 2016;11(7):e0159044.
  • Busch J, Ralla B, Jung M, et al. Piwi-interacting RNAs as novel prognostic markers in clear cell renal cell carcinomas. J Exp Clin Cancer Res. 2015b;34(1):61.
  • Busch J, Ralla B, Jung M, et al. Piwi-interacting RNAs as novel prognostic markers in clear cell renal cell carcinomas. J Exp Clin Cancer Res. 2015a;34(1):1–11.
  • Chang Z, Ji G, Huang R, et al. PIWI-interacting RNAs piR-13643 and piR-21238 are promising diagnostic biomarkers of papillary thyroid carcinoma. Aging (Albany NY). 2020;12(10):9292.
  • Han H, Fan G, Song S, et al. piRNA-30473 contributes to tumorigenesis and poor prognosis by regulating m6A RNA methylation in DLBCL. Blood. 2021;137(12):1603–1614.
  • Litwin M, Szczepańska‑Buda A, Piotrowska A, et al. The meaning of PIWI proteins in cancer development. Oncol Lett. 2017;13(5):3354–3362.
  • Qiao D, Zeeman A-M, Deng W, et al. Molecular characterization of hiwi, a human member of the piwi gene family whose overexpression is correlated to seminomas. Oncogene. 2002;21(25):3988–3999.
  • Gao C-L, Sun R, Li D-H, et al. PIWI-like protein 1 upregulation promotes gastric cancer invasion and metastasis. Onco Targets Ther. 2018;11:8783.
  • Wang Y, Liu Y, Shen X, et al. The PIWI protein acts as a predictive marker for human gastric cancer. Int J Clin Exp Pathol. 2012;5(4):315.
  • Genzor P, Cordts SC, Bokil NV, et al. (2019). Aberrant expression of select piRNA-pathway genes does not reactivate piRNA silencing in cancer cells. Proceedings of the National Academy of Sciences,USA, 116( 23), 11111–11112.
  • Li F, Yuan P, Rao M, 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.
  • Shi S, Yang -Z-Z, Liu S, et al. (2020). PIWIL1 promotes gastric cancer via a piRNA-independent mechanism. Proceedings of the National Academy of Sciences, USA, 117( 36), 22390–22401.
  • Gou L-T, Kang J-Y, Dai P, et al. Ubiquitination-deficient mutations in human Piwi cause male infertility by impairing histone-to-protamine exchange during spermiogenesis. cell. 2017;169(6):1090–1104. e1013.
  • Su C, Ren Z-J, Wang F, et al. 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.
  • Litwin M, Dubis J, Arczyńska K, et al. Correlation of HIWI and HILI expression with cancer stem cell markers in colorectal cancer. Anticancer Res. 2015;35(6):3317–3324.
  • Martinez VD, Enfield KS, Rowbotham DA, et al. An atlas of gastric PIWI-interacting RNA transcriptomes and their utility for identifying signatures of gastric cancer recurrence. Gastric Cancer. 2016;19(2):660–665.
  • Sugimoto K, Kage H, Aki N, et al. The induction of H3K9 methylation by PIWIL4 at the p16Ink4a locus. Biochem Biophys Res Commun. 2007;359(3):497–502.
  • Liang D, Yang Y, Liu Y. The role Hiwi gene in the maintenance of lung cancer stem cell populations. Neoplasma. 2013. DOI:10.4149/neo_2014_022
  • Singh G, Roy J, Rout P, et al. Genome-wide profiling of the PIWI-interacting RNA-mRNA regulatory networks in epithelial ovarian cancers. PLoS One. 2018;13(1):e0190485.
  • Lu Y, Zhang K, Li C, et al. Piwil2 suppresses p53 by inducing phosphorylation of signal transducer and activator of transcription 3 in tumor cells. PLoS One. 2012;7(1):e30999.
  • Network CGAR. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature. 2008;455(7216):1061.
  • Taubert H, Greither T, Kaushal D, 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(7):1098–1100.
  • Sun G, Wang Y, Sun L, et al. Clinical significance of Hiwi gene expression in gliomas. Brain Res. 2011;1373:183–188.
  • Ye Y, Yin D-T, Chen L, et al. Identification of Piwil2-like (PL2L) proteins that promote tumorigenesis. PLoS One. 2010;5(10):e13406.
  • Oh S-J, Kim S-M, Kim Y-O, et al. Clinicopathologic implications of PIWIL2 expression in colorectal cancer. Korean J Pathol. 2012;46(4):318.
  • Yan Z, Qu L-K, Lin M, et al. HIWI expression profile in cancer cells and its prognostic value for patients with colorectal cancer. Chin Med J (Engl). 2011;124(14):2144–2149.
  • Xie Y, Yang Y, Ji D, et al. Hiwi downregulation, mediated by shRNA, reduces the proliferation and migration of human hepatocellular carcinoma cells. Mol Med Rep. 2015;11(2):1455–1461.
  • Lee JH, Jung C, Javadian-Elyaderani P, 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.
  • Klein JD, Qu C, Yang X, et al. c-Fos repression by piwi regulates Drosophila ovarian germline formation and tissue morphogenesis. PLoS Genet. 2016;12(9):e1006281.
  • He G, Chen L, Ye Y, 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.
  • Jiang L, Wang W-J, Li Z-W, et al. Downregulation of Piwil3 suppresses cell proliferation, migration and invasion in gastric cancer. Cancer Biomarkers. 2017;20(4):499–509.
  • Wang D-W, Wang Z-H, Wang -L-L, et al. Overexpression of hiwi promotes growth of human breast cancer cells. Asian Pac J Cancer Prev. 2014;15(18):7553–7558.
  • Qu X, Liu J, Zhong X, et al. PIWIL2 promotes progression of non-small cell lung cancer by inducing CDK2 and Cyclin A expression. J Transl Med. 2015;13(1):301.
  • Li L, Yu C, Gao H, et al. Argonaute proteins: potential biomarkers for human colon cancer. BMC Cancer. 2010;10(1):38.
  • Liu Y, Dou M, Song X, et al. The emerging role of the piRNA/piwi complex in cancer. Mol Cancer. 2019;18(1):123.
  • Sai Lakshmi S, Agrawal S. piRNABank: a web resource on classified and clustered Piwi-interacting RNAs. Nucleic Acids Res. 2008;36(suppl_1):D173–D177.
  • Han Y-N, Li Y, Xia S-Q, et al. PIWI proteins and PIWI-interacting RNA: emerging roles in cancer. Cell Physiol Biochem. 2017;44(1):1–20.
  • Wang J, Zhang P, Lu Y, et al. piRBase: a comprehensive database of piRNA sequences. Nucleic Acids Res. 2019;47(D1):D175–D180.
  • Williams KP, Lau BY. RNAcentral: a comprehensive database of non-coding RNA sequences. Nucleic Acids Res. 2016;45:SAND-2017-0752J.
  • Wang X, Tong X, Gao H, et al. Silencing HIWI suppresses the growth, invasion and migration of glioma cells. Int J Oncol. 2014;45(6):2385–2392.
  • Wang Z, Ma K, Pitts S, et al. Novel circular RNA circNF1 acts as a molecular sponge, promoting gastric cancer by absorbing miR-16. Endocr Relat Cancer. 2019;26(3):265–277.
  • Xin J, Du M, Jiang X, et al. Systematic evaluation of the effects of genetic variants on PIWI-interacting RNA expression across 33 cancer types. Nucleic Acids Res. 2021;49(1):90–97.