CoChat
Sign Up
Cited by 90Cancer-related molecular mechanisms researchEpigenetics and DNA MethylationRNA modifications and cancer

The epigenetic regulatory mechanism of PIWI/piRNAs in human cancers

Open access
Zhang, Qun, Zhu, Yazhi, Cao, Xinyu, Tan, Wenhui, Yu, Jianglong, Lu, Yaqiong, Kang, Ran, Wang, Xiaolan +1 more·2023·Molecular Cancer
DOI 10.1186/s12943-023-01749-3PMC PMC9990219
Open this paper in CoChat — free accountOpen PDF

Abstract

PIWI proteins have a strong correlation with PIWI-interacting RNAs (piRNAs), which are significant in development and reproduction of organisms. Recently, emerging evidences have indicated that apart from the reproductive function, PIWI/piRNAs with abnormal expression, also involve greatly in varieties of human cancers. Moreover, human PIWI proteins are usually expressed only in germ cells and hardly in somatic cells, so the abnormal expression of PIWI proteins in different types of cancer offer a promising opportunity for precision medicine. In this review, we discussed current researches about the biogenesis of piRNA, its epigenetic regulatory mechanisms in human cancers, such as N6-methyladenosine (m 6 A) methylation, histone modifications, DNA methylation and RNA interference, providing novel insights into the markers for clinical diagnosis, treatment and prognosis in human cancers.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1186/s12943-023-01749-3

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • piRNAs regulate epigenetic mechanisms involved in germ cell development.

    “piRNAs regulate epigenetic mechanisms involved in germ cell development, and inaccurately, this kind of ncRNA has been only categorized in animals, while the correct definition is within the metazoans group [68,69].”

    From Revisiting Epigenetics Fundamentals and Its Biomedical Implications (2024) · cites this paper as [68]

  • piRNAs have been incorrectly categorized only in animals; the correct definition is within the metazoans group.

    “piRNAs regulate epigenetic mechanisms involved in germ cell development, and inaccurately, this kind of ncRNA has been only categorized in animals, while the correct definition is within the metazoans group [68,69].”

    From Revisiting Epigenetics Fundamentals and Its Biomedical Implications (2024) · cites this paper as [68]

    The Introduction’s ‘Overview of piRNAs’ describes piRNAs in Drosophila, invertebrates, and vertebrates, but does not say that categorizing them in animals is incorrect or that ‘metazoans’ is the correct definition. Searches for those classification terms found no passage addressing the claimed correction. (LLM, conf=0.74)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 137 · Cited by 90

Research works printed but not linked: 128

  1. [1]Huang H Yu X Han X Hao J Zhao J Bebek G Piwil1 Regulates Glioma Stem Cell Maintenance and Glioblastoma Progression Cell Rep 2021 34 1 108522 10.1016/j.celrep.2020.108522 33406417 PMC7837390 · DOI
  2. [2]Thomson T Lin H The biogenesis and function of PIWI proteins and piRNAs: progress and prospect Annu Rev Cell Dev Biol 2009 25 355 376 10.1146/annurev.cellbio.24.110707.175327 19575643 PMC2780330 · DOI
  3. [3]Cerutti L Mian N Bateman A Domains in gene silencing and cell differentiation proteins: the novel PAZ domain and redefinition of the Piwi domain Trends Biochem Sci 2000 25 10 481 2 10.1016/s0968-0004(00)01641-8 11050429 · DOI
  4. [4]Yamaguchi S Oe A Nishida KM Yamashita K Kajiya A Hirano S Crystal structure of Drosophila Piwi Nature communications 2020 11 1 858 10.1038/s41467-020-14687-1 32051406 PMC7015924 · DOI
  5. [5]Carmell MA Xuan Z Zhang MQ Hannon GJ The Argonaute family: tentacles that reach into RNAi, developmental co ntrol, stem cell maintenance, and tumorigenesis Genes Dev 2002 16 21 2733 42 10.1101/gad.1026102 12414724 · DOI
  6. [6]Couvillion MT Lee SR Hogstad B Malone CD Tonkin LA Sachidanandam R Sequence, biogenesis, and function of diverse small RNA classes bound to the Piwi family proteins of Tetrahymena thermophila Genes Dev 2009 23 17 2016 2032 10.1101/gad.1821209 19656801 PMC2751968 · DOI
  7. [7]Shi S Yang ZZ Liu S Yang F Lin H PIWIL1 promotes gastric cancer via a piRNA-independent mechanism Proc Natl Acad Sci USA 2020 117 36 22390 22401 10.1073/pnas.2008724117 32848063 PMC7486755 · DOI
  8. [8]Song JJ Smith SK Hannon GJ Joshua-Tor L Crystal structure of Argonaute and its implications for RISC slicer activity Science 2004 305 5689 1434 1437 10.1126/science.1102514 15284453 · DOI
  9. [9]Kim VN Han J Siomi MC Biogenesis of small RNAs in animals Nat Rev Mol Cell Biol 2009 10 2 126 139 10.1038/nrm2632 19165215 · DOI
  10. [10]Mao Y Ni N Huang L Fan J Wang H He F Argonaute (AGO) proteins play an essential role in mediating BMP9-induced osteogenic signaling in mesenchymal stem cells (MSCs) Genes & diseases 2021 8 6 918 930 10.1016/j.gendis.2021.04.004 34522718 PMC8427325 · DOI
  11. [11]Shi CY Kingston ER Kleaveland B Lin DH Stubna MW Bartel DP The ZSWIM8 ubiquitin ligase mediates target-directed microRNA degradation Science (New York, NY) 2020 370 6523 eabc9359 10.1126/science.abc9359 PMC8356967 33184237 · DOI
  12. [12]Bamezai S Rawat VP Buske C Concise review: The Piwi-piRNA axis: pivotal beyond transposon silencing Stem Cells 2012 30 12 2603 2611 10.1002/stem.1237 22996918 · DOI
  13. [13]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 10.7150/ijbs.68221 35637965 PMC9134905 · DOI
  14. [14]Sasaki T Shiohama A Minoshima S Shimizu N Identification of eight members of the Argonaute family in the human g enome Genomics 2003 82 3 323 30 10.1016/s0888-7543(03)00129-0 12906857 · DOI
  15. [15]Gunawardane LS Saito K Nishida KM Miyoshi K Kawamura Y Nagami T A slicer-mediated mechanism for repeat-associated siRNA 5' end formati on in Drosophila Science (New York, NY) 2007 315 5818 1587 90 10.1126/science.1140494 17322028 · DOI
  16. [16]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 10.1126/science.1129333 16809489 · DOI
  17. [17]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 U S A 2019 116 23 11111 11112 10.1073/pnas.1904498116 31110013 PMC6561285 · DOI
  18. [18]Qiao D Zeeman A-M Deng W Looijenga LHJ Lin H Molecular characterization of hiwi, a human member of the piwi gene fa mily whose overexpression is correlated to seminomas Oncogene 2002 21 25 3988 99 10.1038/sj.onc.1205505 12037681 · DOI
  19. [19]Mei Y Clark D Mao L Novel dimensions of piRNAs in cancer Cancer Lett 2013 336 1 46 52 10.1016/j.canlet.2013.04.008 23603435 PMC3707114 · DOI
  20. [20]Liu Y Dou M Song X Dong Y Liu S Liu H The emerging role of the piRNA/piwi complex in cancer Mol Cancer 2019 18 1 123 10.1186/s12943-019-1052-9 31399034 PMC6688334 · DOI
  21. [21]Jia R He X Ma W Lei Y Cheng H Sun H Aptamer-Functionalized Activatable DNA Tetrahedron Nanoprobe for PIWI-Interacting RNA Imaging and Regulating in Cancer Cells Anal Chem 2019 91 23 15107 15113 10.1021/acs.analchem.9b03819 31691558 · DOI
  22. [22]Ali SD Tayara H Chong KT Identification of piRNA disease associations using deep learning Comput Struct Biotechnol J 2022 20 1208 1217 10.1016/j.csbj.2022.02.026 35317234 PMC8908038 · DOI
  23. [23]Weng W Li H Goel A Piwi-interacting RNAs (piRNAs) and cancer: Emerging biological concepts and potential clinical implications Biochim Biophys Acta Rev Cancer 2019 1871 1 160 169 10.1016/j.bbcan.2018.12.005 30599187 PMC6392428 · DOI
  24. [24]Cornes E Bourdon L Singh M Mueller F Quarato P Wernersson E piRNAs initiate transcriptional silencing of spermatogenic genes during C. elegans germline development Developmental cell 2022 57 2 180 96e7 10.1016/j.devcel.2021.11.025 34921763 PMC8796119 · DOI
  25. [25]Aravin A Gaidatzis D Pfeffer S Lagos-Quintana M Landgraf P Iovino N A novel class of small RNAs bind to MILI protein in mouse testes Nature 2006 442 7099 203 207 10.1038/nature04916 16751777 · DOI · Paper page
  26. [26]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 10.1038/s41576-018-0073-3 30446728 · DOI
  27. [27]Zeng Y Qu L-K Meng L Liu C-Y Dong B Xing X HIWI expression profile in cancer cells and its prognostic value for patients with colorectal cancer Chin Med J 2011 124 14 2144 9 21933617
  28. [28]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 10.1038/nature04917 16751776 · DOI · Paper page
  29. [29]Gebert D Neubert LK Lloyd C Gui J Lehmann R Teixeira FK Large Drosophila germline piRNA clusters are evolutionarily labile and dispensable for transposon regulation Mol Cell 2021 81 19 3965 78.e5 10.1016/j.molcel.2021.07.011 34352205 PMC8516431 · DOI
  30. [30]Robine N Lau NC Balla S Jin Z Okamura K Kuramochi-Miyagawa S A broadly conserved pathway generates 3'UTR-directed primary piRNAs Current biology: CB 2009 19 24 2066 2076 10.1016/j.cub.2009.11.064 20022248 PMC2812478 · DOI
  31. [31]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 10.1038/nature11502 23064227 PMC3493678 · DOI
  32. [32]Jensen S Brasset E Parey E RoestCrollius H Sharakhov IV Vaury C Conserved Small Nucleotidic Elements at the Origin of Concerted piRNA Biogenesis from Genes and lncRNAs Cells 2020 9 6 1491 10.3390/cells9061491 32570966 PMC7349650 · DOI
  33. [33]Houwing S Kamminga LM Berezikov E Cronembold D Girard A van den Elst H A role for Piwi and piRNAs in germ cell maintenance and transposon silencing in Zebrafish Cell 2007 129 1 69 82 10.1016/j.cell.2007.03.026 17418787 · DOI
  34. [34]Pillai RS Chuma S piRNAs and their involvement in male germline development in mice Dev Growth Differ 2012 54 1 78 92 10.1111/j.1440-169X.2011.01320.x 22221002 · DOI
  35. [35]Senti KA Jurczak D Sachidanandam R Brennecke J piRNA-guided slicing of transposon transcripts enforces their transcriptional silencing via specifying the nuclear piRNA repertoire Genes Dev 2015 29 16 1747 1762 10.1101/gad.267252.115 26302790 PMC4561483 · DOI
  36. [36]Klattenhoff C Theurkauf W Biogenesis and germline functions of piRNAs Development (Cambridge, England) 2008 135 1 3 9 10.1242/dev.006486 18032451 · DOI
  37. [37]Zamore PD Somatic piRNA biogenesis The EMBO J 2010 29 19 3219 21 10.1038/emboj.2010.232 20924396 PMC2957218 · DOI
  38. [38]Nishimasu H Ishizu H Saito K Fukuhara S Kamatani MK Bonnefond L Structure and function of Zucchini endoribonuclease in piRNA biogenesis Nature 2012 491 7423 284 7 10.1038/nature11509 23064230 · DOI
  39. [39]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 Reports 2021 36 9 109640 10.1016/j.celrep.2021.109640 34469728 PMC8459939 · DOI
  40. [40]Nishimura T Nagamori I Nakatani T Izumi N Tomari Y Kuramochi-Miyagawa S PNLDC1, mouse pre-piRNA Trimmer, is required for meiotic and post-meio tic male germ cell development EMBO Rep 2018 19 3 e44957 10.15252/embr.201744957 29444933 PMC5836094 · DOI
  41. [41]Gainetdinov I Colpan C Cecchini K Arif A Jouravleva K Albosta P Terminal modification, sequence, length, and PIWI-protein identity determine piRNA stability Mol Cell 2021 81 23 4826 42.e8 10.1016/j.molcel.2021.09.012 34626567 PMC8642287 · DOI
  42. [42]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 90.e5 10.1016/j.molcel.2018.08.007 30193099 PMC6130920 · DOI
  43. [43]Sato K Siomi MC The piRNA pathway in Drosophila ovarian germ and somatic cells Proc Jpn Acad Ser B Phys Biol Sci 2020 96 1 32 42 10.2183/pjab.96.003 31932527 PMC6974405 · DOI
  44. [44]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 10.1038/s41580-022-00528-0 36104626 · DOI
  45. [45]Izumi N Shoji K Suzuki Y Katsuma S Tomari Y Zucchini consensus motifs determine the mechanism of pre-piRNA production Nature 2020 578 7794 311 316 10.1038/s41586-020-1966-9 31996847 · DOI
  46. [46]Ge DT Wang W Tipping C Gainetdinov I Weng Z Zamore PD The RNA-Binding ATPase, Armitage, Couples piRNA Amplification in Nuage to Phased piRNA Production on Mitochondria Mol Cell 2019 74 5 982 95.e6 10.1016/j.molcel.2019.04.006 31076285 PMC6636356 · DOI
  47. [47]Zhang P Kang JY Gou LT Wang J Xue Y Skogerboe G MIWI and piRNA-mediated cleavage of messenger RNAs in mouse testes Cell Res 2015 25 2 193 207 10.1038/cr.2015.4 25582079 PMC4650574 · DOI
  48. [48]Pek JW Patil VS Kai T piRNA pathway and the potential processing site, the nuage, in the Drosophila germline Dev Growth Differ 2012 54 1 66 77 10.1111/j.1440-169x.2011.01316.x 23741748 · DOI
  49. [49]Lin H piRNAs in the germ line Science (New York, NY) 2007 316 5823 397 10.1126/science.1137543 17446387 · DOI
  50. [50]Ramat A Garcia-Silva MR Jahan C Naït-Saïdi R Dufourt J Garret C The PIWI protein Aubergine recruits eIF3 to activate translation in the germ plasm Cell Res 2020 30 5 421 435 10.1038/s41422-020-0294-9 32132673 PMC7196074 · DOI
  51. [51]Su JF Concilla A Zhang DZ Zhao F Shen FF Zhang H PIWI-interacting RNAs: Mitochondria-based biogenesis and functions in cancer Genes Dis 2021 8 5 603 622 10.1016/j.gendis.2020.09.006 34291132 PMC8278532 · DOI
  52. [52]Czech B Munafò M Ciabrelli F Eastwood EL Fabry MH Kneuss E piRNA-Guided Genome Defense: From Biogenesis to Silencing Annu Rev Genet 2018 52 131 157 10.1146/annurev-genet-120417-031441 30476449 PMC10784713 · DOI
  53. [53]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 10.1016/j.tibs.2015.12.008 26810602 PMC4819955 · DOI
  54. [54]Faehnle CR Joshua-Tor L Argonautes confront new small RNAs Curr Opin Chem Biol 2007 11 5 569 577 10.1016/j.cbpa.2007.08.032 17928262 PMC2077831 · DOI
  55. [55]Shen L Yu C Gao F Hong YT PIWI/piRNA complex-mediated regulation of spermatogenesis Zhonghua Nan Ke Xue=National J Androl 2021 27 3 262 8 34914310
  56. [56]Iwasaki YW Siomi MC Siomi H PIWI-Interacting RNA: Its Biogenesis and Functions Annu Rev Biochem 2015 84 405 433 10.1146/annurev-biochem-060614-034258 25747396 · DOI
  57. [57]Miró-Pina C Charmant O Kawaguchi T Holoch D Michaud A Cohen I Paramecium Polycomb repressive complex 2 physically interacts with the small RNA-binding PIWI protein to repress transposable elements Dev Cell 2022 57 8 1037 52.e8 10.1016/j.devcel.2022.03.014 35429435 · DOI
  58. [58]Reuter M Berninger P Chuma S Shah H Hosokawa M Funaya C Miwi catalysis is required for piRNA amplification-independent LINE1 transposon silencing Nature 2011 480 7376 264 267 10.1038/nature10672 22121019 · DOI
  59. [59]Henderson IR Deleris A Wong W Zhong X Chin HG Horwitz GA The de novo cytosine methyltransferase DRM2 requires intact UBA domains and a catalytically mutated paralog DRM3 during RNA-directed DNA methylation in Arabidopsis thaliana PLoS genetics 2010 6 10 e1001182 10.1371/journal.pgen.1001182 21060858 PMC2965745 · DOI
  60. [60]Botezatu A Socolov R Socolov D Iancu IV Anton G Methylation pattern of methylene tetrahydrofolate reductase and small nuclear ribonucleoprotein polypeptide N promoters in oligoasthenospermia: a case-control study Reprod Biomed Online 2014 28 2 225 231 10.1016/j.rbmo.2013.10.010 24365028 · DOI
  61. [61]Zhang GW Wang L Chen H Guan J Wu Y Zhao J Promoter hypermethylation of PIWI/piRNA pathway genes associated with diminished pachytene piRNA production in bovine hybrid male sterility Epigenetics 2020 15 9 914 931 10.1080/15592294.2020.1738026 32141383 PMC7518677 · DOI
  62. [62]Spichal M Heestand B Billmyre KK Frenk S Mello CC Ahmed S Germ granule dysfunction is a hallmark and mirror of Piwi mutant steri lity Nat Commun 2021 12 1 1420 10.1038/s41467-021-21635-0 33658512 PMC7930041 · DOI
  63. [63]Smallwood SA Kelsey G De novo DNA methylation: a germ cell perspective Trends in genetics: TIG 2012 28 1 33 42 10.1016/j.tig.2011.09.004 22019337 · DOI · Paper page
  64. [64]Zoch A Auchynnikava T Berrens RV Kabayama Y Schöpp T Heep M SPOCD1 is an essential executor of piRNA-directed de novo DNA methylation Nature 2020 584 7822 635 639 10.1038/s41586-020-2557-5 32674113 PMC7612247 · DOI
  65. [65]De Fazio S Bartonicek N Di Giacomo M Abreu-Goodger C Sankar A Funaya C The endonuclease activity of Mili fuels piRNA amplification that silences LINE1 elements Nature 2011 480 7376 259 263 10.1038/nature10547 22020280 · DOI
  66. [66]Wang W Han BW Tipping C Ge DT Zhang Z Weng Z Slicing and Binding by Ago3 or Aub Trigger Piwi-Bound piRNA Production by Distinct Mechanisms Mol Cell 2015 59 5 819 830 10.1016/j.molcel.2015.08.007 26340424 PMC4560842 · DOI
  67. [67]Gao XQ Zhang YH Liu F Ponnusamy M Zhao XM Zhou LY The piRNA CHAPIR regulates cardiac hypertrophy by controlling METTL3-dependent N(6)-methyladenosine methylation of Parp10 mRNA Nat Cell Biol 2020 22 11 1319 1331 10.1038/s41556-020-0576-y 33020597 · DOI
  68. [68]Gou LT Dai P Yang JH Xue Y Hu YP Zhou Y Pachytene piRNAs instruct massive mRNA elimination during late spermiogenesis Cell Res 2015 25 2 266 10.1038/cr.2015.14 25645811 PMC4650571 · DOI
  69. [69]Yin J Jiang XY Qi W Ji CG Xie XL Zhang DX piR-823 contributes to colorectal tumorigenesis by enhancing the transcriptional activity of HSF1 Cancer Sci 2017 108 9 1746 1756 10.1111/cas.13300 28618124 PMC5581525 · DOI
  70. [70]Zhao S Gou LT Zhang M Zu LD Hua MM Hua Y piRNA-triggered MIWI ubiquitination and removal by APC/C in late spermatogenesis Dev Cell 2013 24 1 13 25 10.1016/j.devcel.2012.12.006 23328397 · DOI
  71. [72]Takahashi T Heaton SM Parrish NF Mammalian antiviral systems directed by small RNA PLoS Pathog 2021 17 12 e1010091 10.1371/journal.ppat.1010091 34914813 PMC8675686 · DOI
  72. [73]Moody SC Wakitani S Young JC Western PS Loveland KL Evidence that activin A directly modulates early human male germline differentiation status Reproduction (Cambridge, England) 2020 160 1 141 154 10.1530/rep-20-0095 32484162 · DOI
  73. [74]Rounge TB Furu K Skotheim RI Haugen TB Grotmol T Enerly E Profiling of the small RNA populations in human testicular germ cell tumors shows global loss of piRNAs Mol Cancer 2015 14 153 10.1186/s12943-015-0411-4 26265322 PMC4533958 · DOI
  74. [75]Ferreira HJ Heyn H Garcia del Muro X Vidal A Larriba S Muñoz C Epigenetic loss of the PIWI/piRNA machinery in human testicular tumorigenesis Epigenetics 2014 9 1 113 8 10.4161/epi.27237 24247010 PMC3928173 · DOI
  75. [76]Jeyapalan JN Noor DA Lee SH Tan CL Appleby VA Kilday JP Methylator phenotype of malignant germ cell tumours in children identifies strong candidates for chemotherapy resistance Br J Cancer 2011 105 4 575 585 10.1038/bjc.2011.218 21712824 PMC3170957 · DOI
  76. [77]Halajzadeh J Dana PM Asemi Z Mansournia MA Yousefi B An insight into the roles of piRNAs and PIWI proteins in the diagnosis and pathogenesis of oral, esophageal, and gastric cancer Pathol Res Pract 2020 216 10 153112 10.1016/j.prp.2020.153112 32853949 · DOI
  77. [78]Aoyama T Yamashita S Tomita K Mechanistic insights into m6A modification of U6 snRNA by human METTL16 Nucleic Acids Res 2020 48 9 5157 5168 10.1093/nar/gkaa227 32266935 PMC7229813 · DOI
  78. [79]Meyer KD Jaffrey SR Rethinking m(6)A Readers, Writers, and Erasers Annu Rev Cell Dev Biol 2017 33 319 342 10.1146/annurev-cellbio-100616-060758 28759256 PMC5963928 · DOI
  79. [80]Schwartz S Mumbach MR Jovanovic M Wang T Maciag K Bushkin GG Perturbation of m6A writers reveals two distinct classes of mRNA methylation at internal and 5' sites Cell Rep 2014 8 1 284 296 10.1016/j.celrep.2014.05.048 24981863 PMC4142486 · DOI
  80. [81]Wen J Lv R Ma H Shen H He C Wang J Zc3h13 Regulates Nuclear RNA m(6)A Methylation and Mouse Embryonic Stem Cell Self-Renewal Mol Cell 2018 69 6 1028 38 e6 10.1016/j.molcel.2018.02.015 29547716 PMC5858226 · DOI
  81. [83]Wang S Gao S Zeng Y Zhu L Mo Y Wong CC N6-Methyladenosine Reader YTHDF1 Promotes ARHGEF2 Translation and RhoA Signaling in Colorectal Cancer Gastroenterology 2022 162 4 1183 1196 10.1053/j.gastro.2021.12.269 34968454 · DOI
  82. [84]Xie Q Li Z Luo X Wang D Zhou Y Zhao J piRNA-14633 promotes cervical cancer cell malignancy in a METTL14-dependent m6A RNA methylation manner J Transl Med 2022 20 1 51 10.1186/s12967-022-03257-2 35093098 PMC8802215 · DOI
  83. [85]Han H Fan G Song S Jiang Y Qian C Zhang W piRNA-30473 contributes to tumorigenesis and poor prognosis by regulating m6A RNA methylation in DLBCL Blood 2021 137 12 1603 1614 10.1182/blood.2019003764 32967010 · DOI
  84. [86]Liu J Chen M Ma L Dang X Du G piRNA-36741 regulates BMP2-mediated osteoblast differentiation via METTL3 controlled m6A modification Aging (Albany NY) 2021 13 19 23361 23375 10.18632/aging.203630 34645714 PMC8544320 · DOI
  85. [88]Jenuwein T Allis CD Translating the histone code Science 2001 293 5532 1074 1080 10.1126/science.1063127 11498575 · DOI · Paper page
  86. [89]Puppin C Passon N Lavarone E Di Loreto C Frasca F Vella V Levels of histone acetylation in thyroid tumors Biochem Biophys Res Commun 2011 411 4 679 683 10.1016/j.bbrc.2011.06.182 21763277 · DOI
  87. [90]Kouzarides T Histone methylation in transcriptional control Curr Opin Genet Dev 2002 12 2 198 209 10.1016/s0959-437x(02)00287-3 11893494 · DOI · Paper page
  88. [92]He X Chen X Zhang X Duan X Pan T Hu Q 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 10.1093/nar/gkv214 25779046 PMC4402533 · DOI
  89. [93]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 10.1002/jcb.25199 26205624 · DOI
  90. [94]Meseure D Vacher S Boudjemaa S Laé M Nicolas A Leclere R Biopathological Significance of PIWI-piRNA Pathway Deregulation in Invasive Breast Carcinomas Cancers 2020 12 10 2833 10.3390/cancers12102833 33008024 PMC7600338 · DOI
  91. [96]Jaenisch R Bird A Epigenetic regulation of gene expression: how the genome integrates in trinsic and environmental signals Nat Genet 2003 33 Suppl 245 54 10.1038/ng1089 12610534 · DOI · Paper page
  92. [97]Rausch C Hastert FD Cardoso MC DNA Modification Readers and Writers and Their Interplay J Mol Biol 2019 10.1016/j.jmb.2019.12.018 31866298 · DOI
  93. [98]Baylin SB Herman JG Graff JR Vertino PM Issa JP Alterations in DNA methylation: a fundamental aspect of neoplasia Adv Cancer Res 1998 72 141 196 10.1016/S0065-230X(08)60702-2 9338076 · DOI
  94. [99]Ko M An J Pastor WA Koralov SB Rajewsky K Rao A TET proteins and 5-methylcytosine oxidation in hematological cancers Immunol Rev 2015 263 1 6 21 10.1111/imr.12239 25510268 PMC4617313 · DOI
  95. [100]Zardo G The Role of H3K4 Trimethylation in CpG Islands Hypermethylation in Cancer Biomolecules 2021 11 2 143 10.3390/biom11020143 33499170 PMC7912453 · DOI
  96. [101]Miles SA Sandler AD CpG oligonucleotides for immunotherapeutic treatment of neuroblastoma Adv Drug Deliv Rev 2009 61 3 275 82 10.1016/j.addr.2008.12.011 19186194 · DOI
  97. [102]Moore LD Le T Fan G DNA methylation and its basic function Neuropsychopharmacology 2013 38 1 23 38 10.1038/npp.2012.112 22781841 PMC3521964 · DOI · Paper page
  98. [103]Huang W Li H Yu Q Xiao W Wang DO LncRNA-mediated DNA methylation: an emerging mechanism in cancer and beyond J Exp Clin Cancer Res 2022 41 1 100 10.1186/s13046-022-02319-z 35292092 PMC8922926 · DOI
  99. [104]Su J-F Zhao F Gao Z-W Hou Y-J Li Y-Y Duan L-J piR-823 demonstrates tumor oncogenic activity in esophageal squamous c ell carcinoma through DNA methylation induction via DNA methyltransfer ase 3B Pathol Res Pract 2020 216 4 152848 10.1016/j.prp.2020.152848 32051106 · DOI
  100. [105]Liu T Wang J Sun L Li M He X Jiang J Piwi-interacting RNA-651 promotes cell proliferation and migration and inhibits apoptosis in breast cancer by facilitating DNMT1-mediated PTEN promoter methylation Cell cycle (Georgetown, Tex) 2021 20 16 1603 1616 10.1080/15384101.2021.1956090 34313525 PMC8409782 · DOI
  101. [106]Nouri M Massah S Caradec J Lubik AA Li N Truong S Transient Sox9 Expression Facilitates Resistance to Androgen-Targeted Therapy in Prostate Cancer Clin Cancer Res 2020 26 7 1678 1689 10.1158/1078-0432.Ccr-19-0098 31919137 · DOI
  102. [107]Yasumizu Y Rajabi H Jin C Hata T Pitroda S Long MD Author Correction: MUC1-C regulates lineage plasticity driving progression to neuroendocrine prostate cancer Nat Commun 2020 11 1 1095 10.1038/s41467-020-14808-w 32094369 PMC7039914 · DOI
  103. [108]Ding X Li Y Lu J Zhao Q Guo Y Lu Z 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 641052 10.3389/fcell.2021.641052 33791297 PMC8005588 · DOI
  104. [109]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 10.1093/carcin/bgv105 26210741 PMC5006152 · DOI
  105. [110]Lee JH Schütte D Wulf G Füzesi L Radzun HJ Schweyer S 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 10.1093/hmg/ddi430 16377660 · DOI
  106. [111]Li B Hong J Hong M Wang Y Yu T Zang S piRNA-823 delivered by multiple myeloma-derived extracellular vesicles promoted tumorigenesis through re-educating endothelial cells in the tumor environment Oncogene 2019 38 26 5227 38 10.1038/s41388-019-0788-4 30890754 · DOI
  107. [112]Ai L Mu S Sun C Fan F Yan H Qin Y 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 10.1186/s12943-019-1011-5 30979371 PMC6461814 · DOI
  108. [113]Yan H Wu QL Sun CY Ai LS Deng J Zhang L piRNA-823 contributes to tumorigenesis by regulating de novo DNA methylation and angiogenesis in multiple myeloma Leukemia 2015 29 1 196 206 10.1038/leu.2014.135 24732595 · DOI
  109. [114]Zhang L Meng X Pan C Qu F Gan W Xiang Z piR-31470 epigenetically suppresses the expression of glutathione S-transferase pi 1 in prostate cancer via DNA methylation Cell Signal 2020 67 109501 10.1016/j.cellsig.2019.109501 31837464 · DOI
  110. [115]Reeves ME Baldwin ML Aragon R Baldwin S Chen S-T Li X RASSF1C modulates the expression of a stem cell renewal gene, PIWIL1 BMC Research Notes 2012 5 1 239 10.1186/1756-0500-5-239 22591718 PMC3512503 · DOI
  111. [116]Dammann R Takahashi T Pfeifer GP The CpG island of the novel tumor suppressor gene RASSF1A is intensely methylated in primary small cell lung carcinomas Oncogene 2001 20 27 3563 3567 10.1038/sj.onc.1204469 11429703 · DOI
  112. [117]Amaar YG Reeves ME The impact of the RASSF1C and PIWIL1 on DNA methylation: the identification of GMIP as a tumor suppressor Oncotarget 2020 11 45 4082 4092 10.18632/oncotarget.27795 33227088 PMC7665232 · DOI
  113. [118]Wu X Pan Y Fang Y Zhang J Xie M Yang F The Biogenesis and Functions of piRNAs in Human Diseases Mol Ther Nucleic Acids 2020 21 108 120 10.1016/j.omtn.2020.05.023 32516734 PMC7283962 · DOI
  114. [119]Li F Yuan P Rao M Jin CH Tang W Rong YF 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 10.1038/s41556-020-0486-z 32203416 · DOI
  115. [120]Correia de Sousa M Gjorgjieva M Dolicka D Sobolewski C Foti M Deciphering miRNAs' Action through miRNA Editing Int J Mol Sci 2019 20 24 6249 10.3390/ijms20246249 31835747 PMC6941098 · DOI
  116. [121]Ali Syeda Z Langden SSS Munkhzul C Lee M Song SJ Regulatory Mechanism of MicroRNA Expression in Cancer Int J Mol Sci 2020 21 5 1723 10.3390/ijms21051723 32138313 PMC7084905 · DOI
  117. [122]Xiao L Wang J Ju S Cui M Jing R Disorders and roles of tsRNA, snoRNA, snRNA and piRNA in cancer J Med Genet 2022 59 7 623 631 10.1136/jmedgenet-2021-108327 35145038 · DOI
  118. [123]Mei Y Wang Y Kumari P Shetty AC Clark D Gable T A piRNA-like small RNA interacts with and modulates p-ERM proteins in human somatic cells Nat Commun 2015 6 7316 10.1038/ncomms8316 26095918 PMC4557300 · DOI
  119. [124]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 10.18632/oncotarget.15965 28423657 PMC5470966 · DOI
  120. [125]Peng L Song L Liu C Lv X Li X Jie J piR-55490 inhibits the growth of lung carcinoma by suppressing mTOR signaling Tumour biology: the journal of the International Society for Oncodevelopmental Biology and Medicine 2016 37 2 2749 2756 10.1007/s13277-015-4056-0 26408181 · DOI
  121. [126]Weng W Liu N Toiyama Y Kusunoki M Nagasaka T Fujiwara T 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 10.1186/s12943-018-0767-3 29382334 PMC5791351 · DOI
  122. [127]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 50 10.3892/br.2016.628 27123245 PMC4840783 · DOI
  123. [128]Firmino N Martinez VD Rowbotham DA Enfield KSS 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 48 10.1016/j.oraloncology.2016.01.012 26852287 PMC4808439 · DOI
  124. [129]Tan L Mai D Zhang B Jiang X Zhang J Bai R PIWI-interacting RNA-36712 restrains breast cancer progression and che moresistance by interaction with SEPW1 pseudogene SEPW1P RNA Mol Cancer 2019 18 1 9 10.1186/s12943-019-0940-3 30636640 PMC6330501 · DOI
  125. [130]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 10.1002/jcp.29136 31478570 · DOI
  126. [131]Chu H Hui G Yuan L Shi D Wang Y Du M Identification of novel piRNAs in bladder cancer Cancer letters 2015 356 2 Pt B 561 7 10.1016/j.canlet.2014.10.004 25305452 · DOI
  127. [132]Pérez-Herrero E Fernández-Medarde A Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy Eur J Pharm Biopharm 2015 93 52 79 10.1016/j.ejpb.2015.03.018 25813885 · DOI
  128. [133]Shukla SA Bachireddy P Schilling B Galonska C Zhan Q Bango C Cancer-Germline Antigen Expression Discriminates Clinical Outcome to C TLA-4 Blockade Cell 2018 173 3 624 33 e8 10.1016/j.cell.2018.03.026 29656892 PMC6044280 · DOI

Authors
Zhang, Q., Zhu, Y., Cao, X., Tan, W., Yu, J., Lu, Y., Kang, R., Wang, X., & Li, E.
Affiliations
  • University of South China (CN)
  • Chuanshan College University of South China (CN)
  • First Affiliated Hospital of University of South China (CN)
Corresponding author
Li, Ermao
ORCID
Venue
Molecular Cancer
Publisher
Springer Science and Business Media LLC
Published
2023-03-07
Volume
22
Issue
1
Pages
45-45
ISSN
1476-4598 (ISSN-L)
DOI
10.1186/s12943-023-01749-3
PMC
PMC9990219
OpenAlex
W4323364088
Cited by
90
References
137
Citations by year
2026: 19 · 2025: 40 · 2024: 26 · 2023: 5
FWCI
2.84
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Cancer (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Hunan University (18B272, S201910555127, 2020JJ5501)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
Keywords
PIWI proteins, piRNA, epigenetic regulation, human cancer, piRNA biogenesis, N6-methyladenosine methylation, histone modifications, DNA methylation, RNA interference, tumor markers, precision medicine
MeSH terms
Piwi-Interacting RNA, Humans, Neoplasms, DNA Methylation, RNA Interference, Epigenesis, Genetic

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review