1. Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, et al. Cancer statistics in China, 2015. CA Cancer J Clin 2016;66:115-32.
2. Liu Y, Dou M, Song X, Dong Y, Liu S, Liu H, et al. The emerging role of the piRNA/piwi complex in cancer. Mol Cancer 2019;18:123.
3. Klimenko OV. Small non-coding RNAs as regulators of structural evolution and carcinogenesis. Noncoding RNA Res 2017;2:88-92.
4. Chalbatani GM, Dana H, Memari F, Gharagozlou E, Ashjaei S, Kheirandish P, et al. Biological function and molecular mechanism of piRNA in cancer. Pract Lab Med 2019;13:e00113.
5. Navarro A, Tejero R, Vinolas 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;6:31544-56.
6. Ishizu H, Siomi H, Siomi MC. Biology of PIWI-interacting RNAs: new insights into biogenesis and function inside and outside of germlines. Genes Dev 2012;26:2361-73.
7. Litwin M, Szczepanska-Buda A, Piotrowska A, Dziegiel P, Witkiewicz W. The meaning of PIWI proteins in cancer development. Oncol Lett 2017;13:3354-3362.
8. Yu Y, Xiao J, Hann SS. The emerging roles of PIWI-interacting RNA in human cancers. Cancer Manag Res 2019;11:5895-909.
9. Weng W, Li H, Goel A. Piwi-interacting RNAs (piRNAs) and cancer: Emerging biological concepts and potential clinical implications. Biochim Biophys Acta 2019;1871:160-1699.
10. Czech B, Hannon GJ. One loop to rule them all: The ping-pong cycle and piRNA-guided silencing. Trends Biochem Sci 2016;41:324-337.
11. Rajasethupathy P, Antonov I, Sheridan R, Frey S, Sander C, Tuschl T, et al. A role for neuronal piRNAs in the epigenetic control of memory-related synaptic plasticity. Cell 2012;149:693-707.
12. Jacobs DI, Qin Q, Lerro MC, Fu A, Dubrow R, Claus EB, et al. PIWI-interacting RNAs in gliomagenesis: evidence from post-GWAS and functional analyses. Cancer Epidemiol Biomarkers Prev 2016;25:1073-1080.
13. Tamtaji OR, Behnam M, Pourattar MA, Hamblin MR, Mahjoubin-Tehran M, Mirzaei H, et al. PIWI-interacting RNAs and PIWI proteins in glioma: molecular pathogenesis and role as biomarkers. Cell Commun Signal 2020;18:1-11.
14. Masoomabadi N, Gorji A, Ghadiri T, Ebrahimi S. Regulatory role of circular RNAs in the development of therapeutic resistance in the glioma: A double-edged sword. Iran J Basic Med Sci 2025;28:3-15.
15. Jalili-Nik M, Abbasinezhad-Moud F, Sahab-Negah S, Maghrouni A, Etezad Razavi M, Khaleghi Ghadiri M, et al. Antitumor effects of 5-aminolevulinic acid on human malignant glioblastoma cells. Int J Mol Sci 2021;22:5596.
16. Poonaki E, Ariakia F, Jalili-Nik M, Shafiee Ardestani M, Tondro G, Samini F, et al. Targeting BMI-1 with PLGA–PEG nanoparticle-containing PTC209 modulates the behavior of human glioblastoma stem cells and cancer cells. Cancer Nanotechnol 2021;12:5.
17. 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;11:707017.
18. Saito K, Inagaki S, Mituyama T, Kawamura Y, Ono Y, Sakota E, et al. A regulatory circuit for piwi by the large Maf gene traffic jam in Drosophila. Nature 2009;461:1296-1299.
19. Robine N, Lau NC, Balla S, Jin Z, Okamura K, Kuramochi-Miyagawa S, et al. A broadly conserved pathway generates 3’UTR-directed primary piRNAs. Curr Biol 2009;19:2066-2076.
20. 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;157:1364-1379.
21. Chen YA, Stuwe E, Luo Y, Ninova M, Le Thomas A, Rozhavskaya E, et al. Cutoff suppresses RNA polymerase II termination to ensure expression of piRNA precursors. Mol Cell 2016;63:97-109.
22. Le Thomas A, Rogers AK, Webster A, Marinov GK, Liao SE, Perkins EM, et al. Piwi induces piRNA-guided transcriptional silencing and establishment of a repressive chromatin state. Genes Dev 2013;27:390-399.
23. Andersen PR, Tirian L, Vunjak M, Brennecke J. A heterochromatin-dependent transcription machinery drives piRNA expression. Nature 2017;549:54-59.
24. Masuda S, Das R, Cheng H, Hurt E, Dorman N, Reed R. Recruitment of the human TREX complex to mRNA during splicing. Genes Dev. 2005;19:1512-1517.
25. Reed R. Coupling transcription, splicing and mRNA export. Curr Opin Cell Biol 2003;15:326-331.
26. 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;151:871-884.
27. Nishimasu H, Ishizu H, Saito K, Fukuhara S, Kamatani MK, Bonnefond L, et al. Structure and function of Zucchini endoribonuclease in piRNA biogenesis. Nature 2012;491:284-287.
28. 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;491:279-283.
29. 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;71:775-90. e5.
30. Han BW, Wang W, Li C, Weng Z, Zamore PD. Noncoding RNA. piRNA-guided transposon cleavage initiates Zucchini-dependent, phased piRNA production. Science 2015;348:817-821.
31. Iwasaki YW, Siomi MC, Siomi H. PIWI-Interacting RNA: Its Biogenesis and Functions. Annu Rev Biochem 2015;84:405-433.
32. Luteijn MJ, Ketting RF. PIWI-interacting RNAs: from generation to transgenerational epigenetics. Nat Rev Genet 2013;14:523-534.
33. Han BW, Zamore PD. piRNAs. Curr Biol. 2014;24:R730-R733.
34. Ross RJ, Weiner MM, Lin H. PIWI proteins and PIWI-interacting RNAs in the soma. Nature 2014;505:353-359.
35. Zhang P, Kang JY, Gou LT, Wang J, Xue Y, Skogerboe G, et al. MIWI and piRNA-mediated cleavage of messenger RNAs in mouse testes. Cell Res 2015;25:193-207.
36. Stein CB, Genzor P, Mitra S, Elchert AR, Ipsaro JJ, Benner L, et al. Decoding the 5’ nucleotide bias of PIWI-interacting RNAs. Nat Commun 2019;10:828.
37. Zamore PD. Somatic piRNA biogenesis. EMBO J 2010;29:3219-3221.
38. Thomson T, Lin H. The biogenesis and function of PIWI proteins and piRNAs: progress and prospect. Annu Rev Cell Dev Biol 2009;25:355-736.
39. Ernst C, Odom DT, Kutter C. The emergence of piRNAs against transposon invasion to preserve mammalian genome integrity. Nat Commun 2017;8:1411.
40. Czech B, Munafo 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.
41. Zhang S, Pointer B, Kelleher ES. Rapid evolution of piRNA-mediated silencing of an invading transposable element was driven by abundant de novo mutations. Genome Res 2020;30:566-575.
42. Payer LM, Burns KH. Transposable elements in human genetic disease. Nat Rev Genet 2019;20:760-772.
43. Burns KH. Transposable elements in cancer. Nat Rev Cancer 2017;17:415-424.
44. Castel SE, Martienssen RA. RNA interference in the nucleus: roles for small RNAs in transcription, epigenetics and beyond. Nat Rev Genet. 2013;14:100-112.
45. Sienski G, Donertas D, Brennecke J. Transcriptional silencing of transposons by Piwi and maelstrom and its impact on chromatin state and gene expression. Cell 2012;151:964-980.
46. De Fazio S, Bartonicek N, Di Giacomo M, Abreu-Goodger C, Sankar A, Funaya C, et al. The endonuclease activity of Mili fuels piRNA amplification that silences LINE1 elements. Nature 2011;480:259-263.
47. Ninova M, Chen YA, Godneeva B, Rogers AK, Luo Y, Fejes Toth K, et al. Su(var)2-10 and the SUMO Pathway Link piRNA-Guided Target Recognition to Chromatin Silencing. Mol Cell 2020;77:556-570 e6.
48. Neganova ME, Klochkov SG, Aleksandrova YR, Aliev G. Histone modifications in epigenetic regulation of cancer: Perspectives and achieved progress. Semin Cancer Biol 2022;83:452-471.
49. Siddiqi S, Matushansky I. Piwis and piwi-interacting RNAs in the epigenetics of cancer. J Cell Biochem 2012;113:373-380.
50. 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;31:785-799.
51. Sohn EJ, Han ME, Park YM, Kim YH, Oh SO. The potential of piR-823 as a diagnostic biomarker in oncology: A systematic review. PLoS One. 2023;18:e0294685.
52. 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;359:497-502.
53. Anzelon TA, Chowdhury S, Hughes SM, Xiao Y, Lander GC, MacRae IJ. Structural basis for piRNA targeting. Nature 2021;597:285-289.
54. 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;18:3358-3373.
55. Bagga S, Bracht J, Hunter S, Massirer K, Holtz J, Eachus R, et al. Regulation by let-7 and lin-4 miRNAs results in target mRNA degradation. Cell 2005;122:553-563.
56. Bazzini AA, Lee MT, Giraldez AJ. Ribosome profiling shows that miR-430 reduces translation before causing mRNA decay in zebrafish. Science 2012;336:233-237.
57. Agarwal V, Bell GW, Nam JW, Bartel DP. Predicting effective microRNA target sites in mammalian mRNAs. Elife 2015;4.
58. 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;11:1017-1027.
59. Siomi MC, Sato K, Pezic D, Aravin AA. PIWI-interacting small RNAs: the vanguard of genome defence. Nat Rev Mol Cell Biol 2011;12:246-258.
60. 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;31:67-78.
61. Vourekas A, Alexiou P, Vrettos N, Maragkakis M, Mourelatos Z. Sequence-dependent but not sequence-specific piRNA adhesion traps mRNAs to the germ plasm. Nature 2016;531:390-394.
62. 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;172:937-951 e18.
63. 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;619:394-402.
64. Xiao Y, Ke A. PIWI Takes a Giant Step. Cell. 2016;167:310-2.
65. Izumi N, Shoji K, Suzuki Y, Katsuma S, Tomari Y. Zucchini consensus motifs determine the mechanism of pre-piRNA production. Nature 2020;578:311-316.
66. Ramat A, Simonelig M. Functions of PIWI Proteins in Gene Regulation: New Arrows Added to the piRNA Quiver. Trends Genet 2021;37:188-200.
67. Wang W, Han BW, Tipping C, Ge DT, Zhang Z, Weng Z, et al. Slicing and binding by Ago3 or Aub trigger piwi-bound piRNA production by distinct mechanisms. Mol Cell 2015;59:819-830.
68. 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. Tumour Biol 2016;37:2749-2756.
69. 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;13:465.
70. Jin SM, Youle RJ. PINK1- and Parkin-mediated mitophagy at a glance. J Cell Sci 2012;125:795-799.
71. Youle RJ, Narendra DP. Mechanisms of mitophagy. Nat Rev Mol Cell Biol 2011;12:9-14.
72. Komatsu M, Waguri S, Koike M, Sou YS, Ueno T, Hara T, et al. Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice. Cell 2007;131:1149-1163.
73. 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;2018:5848046.
74. Trzybulska D, Vergadi E, Tsatsanis C. miRNA and other non-coding RNAs as promising diagnostic markers. EJIFCC 2018;29:221-226.
75. Meseure D, Drak Alsibai K. Part 2: Deregulated expressions of PIWI proteins and piRNAs as new candidate biomarkers and potential therapeutic tools in cancer. Epigenetics Chromatin 2020.
76. Mei Y, Clark D, Mao L. Novel dimensions of piRNAs in cancer. Cancer Lett 2013;336:46-52.
77. Tan Y, Liu L, Liao M, Zhang C, Hu S, Zou M, et al. Emerging roles for PIWI proteins in cancer. Acta Biochim Biophys Sin (Shanghai) 2015;47:315-324.
78. Ng KW, Anderson C, Marshall EA, Minatel BC, Enfield KS, Saprunoff HL, et al. Piwi-interacting RNAs in cancer: Emerging functions and clinical utility. Mol Cancer 2016;15:5.
79. Liu L, Dai Y, Chen J, Zeng T, Li Y, Chen L, et al. Maelstrom promotes hepatocellular carcinoma metastasis by inducing epithelial-mesenchymal transition by way of Akt/GSK-3beta/Snail signaling. Hepatol 2014;59:531-543.
80. Cheng J, Guo JM, Xiao BX, Miao Y, Jiang Z, Zhou H, et al. piRNA, the new non-coding RNA, is aberrantly expressed in human cancer cells. Clin Chim Acta 2011;412:1621-1625.
81. Hou JM, Krebs M, Ward T, Sloane R, Priest L, Hughes A, et al. Circulating tumor cells as a window on metastasis biology in lung cancer. Am J Pathol 2011;178:989-996.
82. Lambert AW, Pattabiraman DR, Weinberg RA. Emerging biological principles of metastasis. Cell 2017;168:670-691.
83. 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 [Internet] 2015 2015/06//; 34:[61 p.]. Available from: http://europepmc.org/abstract/MED/26071182
https://jeccr.biomedcentral.com/counter/pdf/10.1186/s13046-015-0180-3
https://doi.org/10.1186/s13046-015-0180-3
https://europepmc.org/articles/PMC4467205
https://europepmc.org/articles/PMC4467205?pdf=render.
84. Jacobs DI, Qin Q, Fu A, Chen Z, Zhou J, Zhu Y. piRNA-8041 is downregulated in human glioblastoma and suppresses tumor growth in vitro and in vivo. Oncotarget 2018;9:37616-37626.
85. Brabletz S, Schuhwerk H, Brabletz T, Stemmler MP. Dynamic EMT: A multi-tool for tumor progression. EMBO J 2021;40:e108647.
86. Chen T, You Y, Jiang H, Wang ZZ. Epithelial-mesenchymal transition (EMT): A biological process in the development, stem cell differentiation, and tumorigenesis. J Cell Physiol 2017;232:3261-3272.
87. De Craene B, Berx G. Regulatory networks defining EMT during cancer initiation and progression. Nat Rev Cancer 2013;13:97-110.
88. Pastushenko I, Blanpain C. EMT Transition States during Tumor Progression and Metastasis. Trends Cell Biol 2019;29:212-226.
89. Suski JM, Braun M, Strmiska V, Sicinski P. Targeting cell-cycle machinery in cancer. Cancer Cell 2021;39:759-778.
90. Qian L, Xie H, Zhang L, Zhao Q, Lu J, Yu Z. Piwi-Interacting RNAs: A New Class of Regulator in Human Breast Cancer. Front Oncol 2021;11:695077.
91. Aravin AA, Bourc’his D. Small RNA guides for de novo DNA methylation in mammalian germ cells. Genes Dev. 2008;22:970-5.
92. Siddiqi S, Terry M, Matushansky I. Hiwi mediated tumorigenesis is associated with DNA hypermethylation. PLoS One 2012;7:e33711.
93. 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;29:196-206.
94. 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;17:16.
95. Lee JH, Jung C, Javadian-Elyaderani P, Schweyer S, Schutte D, Shoukier M, et al. Pathways of proliferation and antiapoptosis driven in breast cancer stem cells by stem cell protein piwil2. Cancer Res 2010;70:4569-4579.
96. Lee JH, Schutte D, Wulf G, Fuzesi 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;15:201-211.
97. Kramer A, Schultheis B, Bergmann J, Willer A, Hegenbart U, Ho AD, et al. Alterations of the cyclin D1/pRb/p16(INK4A) pathway in multiple myeloma. Leukemia. 2002;16:1844-51.
98. Wu L, Huang S, Tian W, Liu P, Xie Y, Qiu Y, et al. PIWI-interacting RNA-YBX1 inhibits proliferation and metastasis by the MAPK signaling pathway via YBX1 in triple-negative breast cancer. Cell Death Discov. 2024;10:7.
99. Ullah R, Yin Q, Snell AH, Wan L. RAF-MEK-ERK pathway in cancer evolution and treatment. Semin Cancer Biol 2022;85:123-154.
100. Li D, Luo Y, Gao Y, Yang Y, Wang Y, Xu Y, et al. piR-651 promotes tumor formation in non-small cell lung carcinoma through the upregulation of cyclin D1 and CDK4. Int J Mol Med 2016;38:927-936.
101. 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 2021;20:1603-1616.
102. 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;13:1203821.
103. 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. Carcinog 2015;36:1094-1102.
104. Liu Y, Pan S, Liu L, Zhai X, Liu J, Wen J, et al. A genetic variant in long non-coding RNA HULC contributes to risk of HBV-related hepatocellular carcinoma in a Chinese population. PLoS One 2012;7:e35145.
105. Chen Z, Zhang Y. Role of mammalian DNA methyltransferases in development. Annu Rev Biochem 2020;89:135-158.
106. Lyko F. The DNA methyltransferase family: A versatile toolkit for epigenetic regulation. Nat Rev Genet 2018;19:81-92.
107. Ahmadi Asouri S, Aghadavood E, Mirzaei H, Abaspour A, Esmaeil Shahaboddin M. PIWI-interacting RNAs (PiRNAs) as emerging biomarkers and therapeutic targets in biliary tract cancers: A comprehensive review. Heliyon 2024;10:e33767.
108. Wakisaka KT, Imai Y. The dawn of pirna research in various neuronal disorders. Front Biosci (Landmark Ed) 2019;24:1440-1451.
109. Yang F, Wang PJ. Multiple LINEs of retrotransposon silencing mechanisms in the mammalian germline. Semin Cell Dev Biol 2016;59:118-125.
110. Grivna ST, Beyret E, Wang Z, Lin H. A novel class of small RNAs in mouse spermatogenic cells. Genes Dev 2006;20:1709-1714.
111. Lau NC, Seto AG, Kim J, Kuramochi-Miyagawa S, Nakano T, Bartel DP, et al. Characterization of the piRNA complex from rat testes. Science 2006;313:363-367.
112. Popovic D, Vucic D, Dikic I. Ubiquitination in disease pathogenesis and treatment. Nat Med 2014;20:1242-1253.
113. Deniz O, Frost JM, Branco MR. Regulation of transposable elements by DNA modifications. Nat Rev Genet 2019;20:417-431.
114. 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;9:641052.
115. Samaei NM, Yazdani Y, Alizadeh-Navaei R, Azadeh H, Farazmandfar T. Promoter methylation analysis of WNT/beta-catenin pathway regulators and its association with expression of DNMT1 enzyme in colorectal cancer. J Biomed Sci 2014;21:73.
116. Esteller M, Sparks A, Toyota M, Sanchez-Cespedes M, Capella G, Peinado MA, et al. Analysis of adenomatous polyposis coli promoter hypermethylation in human cancer. Cancer Res 2000;60:4366-4371.
117. Meir Z, Mukamel Z, Chomsky E, Lifshitz A, Tanay A. Single-cell analysis of clonal maintenance of transcriptional and epigenetic states in cancer cells. Nat Genet 2020;52:709-718.
118. Lu Y, Chan YT, Tan HY, Li S, Wang N, Feng Y. Epigenetic regulation in human cancer: The potential role of epi-drug in cancer therapy. Mol Cancer 2020;19:79.
119. Sun T, Wu R, Ming L. The role of m6A RNA methylation in cancer. Biomed Pharmacother 2019;112:108613.
120. Huang H, Weng H, Chen J. The Biogenesis and Precise Control of RNA m(6)A Methylation. Trends Genet 2020;36:44-52.
121. Zhang Y, Geng X, Li Q, Xu J, Tan Y, Xiao M, et al. m6A modification in RNA: Biogenesis, functions and roles in gliomas. J Exp Clin Cancer Res 2020;39:192.
122. Yi YC, Chen XY, Zhang J, Zhu JS. Novel insights into the interplay between m(6)A modification and noncoding RNAs in cancer. Mol Cancer 2020;19:121.
123. Wang K, Zhou LY, Liu F, Lin L, Ju J, Tian PC, et al. PIWI-interacting RNA haapir regulates cardiomyocyte death after myocardial infarction by promoting NAT10-mediated ac(4) C acetylation of Tfec mRNA. Adv Sci (Weinh) 2022;9:e2106058.
124. 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;137:1603-1614.
125. Alarcon CR, Lee H, Goodarzi H, Halberg N, Tavazoie SF. N6-methyladenosine marks primary microRNAs for processing. Nature 2015;519:482-485.
126. Bartosovic M, Molares HC, Gregorova P, Hrossova D, Kudla G, Vanacova S. N6-methyladenosine demethylase FTO targets pre-mRNAs and regulates alternative splicing and 3’-end processing. Nucleic Acids Res 2017;45:11356-11370.
127. Wang H, Zuo H, Liu J, Wen F, Gao Y, Zhu X, et al. Loss of YTHDF2-mediated m(6)A-dependent mRNA clearance facilitates hematopoietic stem cell regeneration. Cell Res 2018;28:1035-1038.
128. Huang H, Weng H, Sun W, Qin X, Shi H, Wu H, et al. Recognition of RNA N(6)-methyladenosine by IGF2BP proteins enhances mRNA stability and translation. Nat Cell Biol 2018;20:285-295.
129. Wang T, Kong S, Tao M, Ju S. The potential role of RNA N6-methyladenosine in Cancer progression. Mol Cancer. 2020;19:88.
130. Su R, Dong L, Li C, Nachtergaele S, Wunderlich M, Qing Y, et al. R-2HG Exhibits Anti-tumor Activity by Targeting FTO/m(6)A/MYC/CEBPA Signaling. Cell 2018;172:90-105 e23.
131. Kwok CT, Marshall AD, Rasko JE, Wong JJ. Genetic alterations of m(6)A regulators predict poorer survival in acute myeloid leukemia. J Hematol Oncol 2017;10:39.
132. Fan K, Fan Z, Cheng H, Huang Q, Yang C, Jin K, et al. Hexokinase 2 dimerization and interaction with voltage-dependent anion channel promoted resistance to cell apoptosis induced by gemcitabine in pancreatic cancer. Cancer Med 2019;8:5903-5915.
133. Shi T, Ma Y, Cao L, Zhan S, Xu Y, Fu F, et al. B7-H3 promotes aerobic glycolysis and chemoresistance in colorectal cancer cells by regulating HK2. Cell Death Dis 2019;10:308.
134. Bhalla K, Jaber S, Nahid MN, Underwood K, Beheshti A, Landon A, et al. Role of hypoxia in Diffuse Large B-cell Lymphoma: Metabolic repression and selective translation of HK2 facilitates development of DLBCL. Sci Rep 2018;8:744.
135. Zhong Y, Tian Y, Wang Y, Bai J, Long Q, Yan L, et al. Small extracellular vesicle piR-hsa-30937 derived from pancreatic neuroendocrine neoplasms upregulates CD276 in macrophages to promote immune evasion. Cancer Immunol Res 2024;12:840-853.
136. Liu HJ, Du H, Khabibullin D, Zarei M, Wei K, Freeman GJ, et al. mTORC1 upregulates B7-H3/CD276 to inhibit antitumor T cells and drive tumor immune evasion. Nat Commun 2023;14:1214.
137. Wang C, Li Y, Jia L, Kim JK, Li J, Deng P, et al. CD276 expression enables squamous cell carcinoma stem cells to evade immune surveillance. Cell Stem Cell 2021;28:1597-613 e7.
138. Picarda E, Ohaegbulam KC, Zang X. Molecular pathways: targeting B7-H3 (CD276) for human cancer immunotherapy. Clin Cancer Res 2016;22:3425-3431.
139. Vitanza NA, Wilson AL, Huang W, Seidel K, Brown C, Gustafson JA, et al. Intraventricular B7-H3 CAR T cells for diffuse intrinsic pontine glioma: Preliminary first-in-human bioactivity and safety. Cancer Discov 2023;13:114-131.
140. Du H, Hirabayashi K, Ahn S, Kren NP, Montgomery SA, Wang X, et al. Antitumor responses in the absence of toxicity in solid tumors by targeting B7-H3 via chimeric antigen receptor T cells. Cancer Cell. 2019;35:221-237 e8.
141. Nielsen SF, Nordestgaard BG, Bojesen SE. Statin use and reduced cancer-related mortality. N Engl J Med 2012;367:1792-1802.
142. Borgquist S, Giobbie-Hurder A, Ahern TP, Garber JE, Colleoni M, Lang I, et al. Cholesterol, cholesterol-lowering medication use, and breast cancer outcome in the BIG 1-98 study. J Clin Oncol 2017;35:1179-1188.
143. Abdel-Rahman O. Statin treatment and outcomes of metastatic pancreatic cancer: a pooled analysis of two phase III studies. Clin Transl Oncol 2019;21:810-816.
144. Zhan Y, Tian F, Fan W, Li X, Wang X, Zhang H, et al. Targeting piRNA-137463 inhibits tumor progression and boosts sensitivity to immune checkpoint blockade via de novo cholesterol biosynthesis in lung adenocarcinoma. Adv Sci (Weinh) 2025;12:e2414100.
145. Ma X, Bi E, Lu Y, Su P, Huang C, Liu L, et al. Cholesterol Induces CD8(+) T Cell Exhaustion in the Tumor Microenvironment. Cell Metab 2019;30:143-156 e5.
146. Paciullo F, Fallarino F, Bianconi V, Mannarino MR, Sahebkar A, Pirro M. PCSK9 at the crossroad of cholesterol metabolism and immune function during infections. J Cell Physiol 2017;232:2330-2338.
147. Villablanca EJ, Raccosta L, Zhou D, Fontana R, Maggioni D, Negro A, et al. Tumor-mediated liver X receptor-alpha activation inhibits CC chemokine receptor-7 expression on dendritic cells and dampens antitumor responses. Nat Med 2010;16:98-105.
148. Roy J, Anand K, Mohapatra S, Nayak R, Chattopadhyay T, Mallick B. Single nucleotide polymorphisms in piRNA-pathway genes: An insight into genetic determinants of human diseases. Mol Genet Genomics 2020;295:1-12.
149. Xu X, Han L, Duan L, Zhao Y, Yang H, Zhou B, et al. Association between eIF3alpha polymorphism and severe toxicity caused by platinum-based chemotherapy in non-small cell lung cancer patients. Br J Clin Pharmacol 2013;75:516-523.
150. Mukherjee P, Bhattacharjee S, Mandal DP. PIWI-interacting RNA (piRNA): A narrative review of its biogenesis, function, and emerging role in lung cancer. Asian Biomed (Res Rev News) 2022;16:3-14.
151. 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.
152. Roy J, Das B, Jain N, Mallick B. PIWI-interacting RNA 39980 promotes tumor progression and reduces drug sensitivity in neuroblastoma cells. J Cell Physiol 2020;235:2286-2299.
153. Dutertre M, Lambert S, Carreira A, Amor-Gueret M, Vagner S. DNA damage: RNA-binding proteins protect from near and far. Trends Biochem Sci 2014;39:141-149.
154. Bamezai S, Pulikkottil AJ, Yadav T, Vegi NM, Mueller J, Mark J, et al. A noncanonical enzymatic function of PIWIL4 maintains genomic integrity and leukemic growth in AML. Blood 2023;142:90-105.
155. Cancer Genome Atlas Research N, Ley TJ, Miller C, Ding L, Raphael BJ, Mungall AJ, et al. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med 2013;368:2059-2074.
156. Ma JB, Yuan YR, Meister G, Pei Y, Tuschl T, Patel DJ. Structural basis for 5’-end-specific recognition of guide RNA by the A. fulgidus Piwi protein. Nature 2005;434:666-670.
157. Yuan YR, Pei Y, Ma JB, Kuryavyi V, Zhadina M, Meister G, et al. Crystal structure of A. aeolicus argonaute, a site-specific DNA-guided endoribonuclease, provides insights into RISC-mediated mRNA cleavage. Mol Cell 2005;19:405-419.
158. Moelling K, Matskevich A, Jung JS. Relationship between retroviral replication and RNA interference machineries. Cold Spring Harb Symp Quant Biol 2006;71:365-368.
159. Garcia-Silva MR, Marquez ME, Pinello N. PIWI pathway: bridging acute myeloid leukemia stemness and cellular differentiation. Front Cell Dev Biol 2024;12:1449353.
160. Gan W, Guan Z, Liu J, Gui T, Shen K, Manley JL, et al. R-loop-mediated genomic instability is caused by impairment of replication fork progression. Genes Dev 2011;25:2041-2056.
161. Iwasaki M, Liedtke M, Gentles AJ, Cleary ML. CD93 Marks a Non-Quiescent Human Leukemia Stem Cell Population and Is Required for Development of MLL-Rearranged Acute Myeloid Leukemia. Cell Stem Cell 2015;17:412-421.
162. Ratan R, Patel SR. Chemotherapy for soft tissue sarcoma. Cancer 2016;122:2952-2960.
163. Tacar O, Sriamornsak P, Dass CR. Doxorubicin: An update on anticancer molecular action, toxicity and novel drug delivery systems. J Pharm Pharmacol 2013;65:157-170.
164. Lin W, Miao Y, Meng X, Huang Y, Zhao W, Ruan J. miRNA-765 mediates multidrug resistance via targeting BATF2 in gastric cancer cells. FEBS Open Bio 2020;10:1021-1030.
165. AbuHammad S, Zihlif M. Gene expression alterations in doxorubicin resistant MCF7 breast cancer cell line. Genomics 2013;101:213-220.
166. Verma H, Singh Bahia M, Choudhary S, Kumar Singh P, Silakari O. Drug metabolizing enzymes-associated chemo resistance and strategies to overcome it. Drug Metab Rev 2019;51:196-223.
167. Wang X, Hui R, Chen Y, Wang W, Chen Y, Gong X, et al. Discovery of Novel Doxorubicin Metabolites in MCF7 Doxorubicin-Resistant Cells. Front Pharmacol 2019;10:1434.
168. Das B, Jain N, Mallick B. piR-39980 mediates doxorubicin resistance in fibrosarcoma by regulating drug accumulation and DNA repair. Commun Biol 2021;4:1312.
169. Hong CC, Tang BK, Hammond GL, Tritchler D, Yaffe M, Boyd NF. Cytochrome P450 1A2 (CYP1A2) activity and risk factors for breast cancer: A cross-sectional study. Breast Cancer Res 2004;6:R352-R365.
170. 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;58:344-357.
171. Hancks DC, Kazazian HH, Jr. Roles for retrotransposon insertions in human disease. Mob DNA 2016;7:9.
172. Elbarbary RA, Lucas BA, Maquat LE. Retrotransposons as regulators of gene expression. Science 2016;351:aac7247.
173. Jang HS, Shah NM, Du AY, Dailey ZZ, Pehrsson EC, Godoy PM, et al. Transposable elements drive widespread expression of oncogenes in human cancers. Nat Genet 2019;51:611-617.
174. Berrens RV, Andrews S, Spensberger D, Santos F, Dean W, Gould P, et al. An endosiRNA-based repression mechanism counteracts transposon activation during global DNA demethylation in embryonic stem cells. Cell Stem Cell 2017;21:694-703 e7.
175. Ariumi Y. Guardian of the human genome: Host defense mechanisms against LINE-1 retrotransposition. Front Chem 2016;4:28.
176. Kishani Farahani R, Soleimanpour S, Golmohammadi M, Soleimanpour-Lichaei HR. PIWIL2 regulates the proliferation, apoptosis and colony formation of colorectal cancer cell line. Iran J Biotechnol 2023;21:e3176.
177. Meseure D, Vacher S, Boudjemaa S, Lae M, Nicolas A, Leclere R, et al. Biopathological significance of PIWI-piRNA pathway deregulation in invasive breast carcinomas. Cancers (Basel) 2020;12:2833.
178. Siomi H, Siomi MC. RNA. Phased piRNAs tackle transposons. Science 2015;348:756-757.
179. Han YN, Li Y, Xia SQ, Zhang YY, Zheng JH, Li W. PIWI proteins and PIWI-interacting RNA: Emerging roles in cancer. Cell Physiol Biochem 2017;44:1-20.
180. Wu X, Pan Y, Fang Y, Zhang J, Xie M, Yang F, et al. The biogenesis and functions of piRNAs in human diseases. Mol Ther Nucleic Acids 2020;21:108-120.
181. Grieco GE, Sebastiani G, Fignani D, Brusco N, Nigi L, Formichi C, et al. Protocol to analyze circulating small non-coding RNAs by high-throughput RNA sequencing from human plasma samples. STAR Protoc 2021;2:100606.
182. Cui L, Lou Y, Zhang X, Zhou H, Deng H, Song H, et al. Detection of circulating tumor cells in peripheral blood from patients with gastric cancer using piRNAs as markers. Clin Biochem 2011;44:1050-1057.
183. Taghizadeh M, Jafari-Koshki T, Jafarlou V, Raeisi M, Alizadeh L, Roosta Y, et al. The role of piRNAs in predicting and prognosing in cancer: a focus on piRNA-823 (a systematic review and meta-analysis). BMC Cancer 2024;24:484.
184. 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;36:6419-6423.
185. 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;18:88.
186. Houwing S, Kamminga LM, Berezikov E, Cronembold D, Girard A, van den Elst H, et al. A role for Piwi and piRNAs in germ cell maintenance and transposon silencing in Zebrafish. Cell 2007;129:69-82.
187. Yang X, Cheng Y, Lu Q, Wei J, Yang H, Gu M. Detection of stably expressed piRNAs in human blood. Int J Clin Exp Med 2015;8:13353-13358.
188. Sarkar A, Ghosh Z. Rejuvenation of piRNAs in emergence of cancer and other diseases. In: Mallick B, editor. AGO-Driven Non-Coding RNAs: Academic Press; 2019. p. 319-33.
189. 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.
190. Saha B, Chakravarty S, Ray S, Saha H, Das K, Ghosh I, et al. Correlating tissue and plasma‑specific piRNA changes to predict their possible role in pancreatic malignancy and chronic inflammation. Biomed Rep 2024;21:186.
191. Peng Q, Chiu PK, Wong CY, Cheng CK, Teoh JY, Ng CF. Identification of piRNA Targets in Urinary Extracellular Vesicles for the Diagnosis of Prostate Cancer. Diagnostics (Basel). 2021;11:1828.
192. 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 (Albany N Y) 2020;12:9292-9310.
193. 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;10:8468-8478.
194. Nakhaei A, Afshari S, Mohatshami E, Jalili-Nik M, Jalali M, Abass KS, et al. Harnessing the connection of the Wnt/beta-catenin pathway and other signaling pathways in glioblastoma multiforme. Crit Rev Oncol Hematol 2026;219:105127.
195. Nakhaei A, Afshari S, Mohammadian M, Ahmadi SS, Mohatshami E, Jalili-Nik M, et al. Harnessing the role of insulin-like growth factor in glioblastoma: A comprehensive review. Neuroscience 2026;594:172-186.
196. Sasmita AO, Wong YP, Ling APK. Biomarkers and therapeutic advances in glioblastoma multiforme. Asia Pac J Clin Oncol 2018;14:40-51.
197. Wesseling P, Capper D. WHO 2016 classification of gliomas. Neuropathol Appl Neurobiol 2018;44:139-150.
198. Ohgaki H, Kleihues P. The definition of primary and secondary glioblastoma. Clin Cancer Res 2013;19:764-772.
199. Ostrom QT, Bauchet L, Davis FG, Deltour I, Fisher JL, Langer CE, et al. The epidemiology of glioma in adults: A “state of the science” review. Neuro Oncol. 2014;16:896-913.
200. Alexander BM, Cloughesy TF. Adult Glioblastoma. J Clin Oncol 2017;35:2402-2409.
201. Hutvagner G, Simard MJ. Argonaute proteins: key players in RNA silencing. Nat Rev Mol Cell Biol 2008;9:22-32.
202. Suzuki R, Honda S, Kirino Y. PIWI Expression and Function in Cancer. Front Genet 2012;3:204.
203. Dong P, Xiong Y, Konno Y, Ihira K, Xu D, Kobayashi N, et al. Critical roles of PIWIL1 in human tumors: Expression, functions, mechanisms, and potential clinical implications. Front Cell Dev Biol 2021;9:656993.
204. Kovalenko TF, Larionova TD, Antipova NV, Shakhparonov MI, Pavlyukov MS. The role of non-coding RNAs in the pathogenesis of glial tumors. Acta Nat 2021;13:38-51.
205. Garcia-Silva MR, Montenegro S, Dacosta S, Tosar JP, Cayota A. PIWIL1 is recruited to centrosomes during mitosis in colorectal cancer cells and is linked to cell cycle progression. Sci Rep 2024;14:23928.
206. 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;34:108522.
207. Presutti D, Ceccarelli M, Micheli L, Papoff G, Santini S, Samperna S, et al. Tis21-gene therapy inhibits medulloblastoma growth in a murine allograft model. PLoS One 2018;13:e0194206.
208. Mullighan CG, Goorha S, Radtke I, Miller CB, Coustan-Smith E, Dalton JD, et al. Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia. Nature 2007;446:758-764.
209. Kuiper RP, Schoenmakers EF, van Reijmersdal SV, Hehir-Kwa JY, van Kessel AG, van Leeuwen FN, et al. High-resolution genomic profiling of childhood ALL reveals novel recurrent genetic lesions affecting pathways involved in lymphocyte differentiation and cell cycle progression. Leukemia 2007;21:1258-1266.
210. Dolezal E, Infantino S, Drepper F, Borsig T, Singh A, Wossning T, et al. The BTG2-PRMT1 module limits pre-B cell expansion by regulating the CDK4-Cyclin-D3 complex. Nat Immunol 2017;18:911-920.
211. Appolloni I, Curreli S, Caviglia S, Barilari M, Gambini E, Pagano A, et al. Role of Btg2 in the Progression of a PDGF-Induced Oligodendroglioma Model. Int J Mol Sci 2012; 13:14667-14678.
212. Moyano M, Stefani G. piRNA involvement in genome stability and human cancer. J Hematol Oncol 2015;8:38.
213. Jiang L, Wang WJ, Li ZW, Wang XZ. Downregulation of Piwil3 suppresses cell proliferation, migration and invasion in gastric cancer. Cancer Biomark 2017;20:499-509.
214. 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;8:1084-1105.
215. Hashim A, Rizzo F, Marchese G, Ravo M, Tarallo R, Nassa G, et al. RNA sequencing identifies specific PIWI-interacting small non-coding RNA expression patterns in breast cancer. Oncotarget 2014;5:9901-9910.
216. 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;15:563-568.
217. Chu H, Hui G, Yuan L, Shi D, Wang Y, Du M, et al. Identification of novel piRNAs in bladder cancer. Cancer Lett 2015;356:561-567.
218. Hallal S, Ebrahim Khani S, Wei H, Lee MYT, Sim HW, Sy J, et al. Deep sequencing of small RNAs from neurosurgical extracellular vesicles substantiates miR-486-3p as a circulating biomarker that distinguishes glioblastoma from lower-grade astrocytoma patients. Int J Mol Sci 2020;21:4954.
219. Nayak R, Chattopadhyay T, Gupta P, Mallick B. Integrative analysis of small non-coding RNAs predicts a piRNA/miRNA-CCND1/BRAF/HRH1/ATXN3 regulatory circuit that drives oncogenesis in glioblastoma. Mol Omics 2023;19:252-261.
220. Dorsam RT, Gutkind JS. G-protein-coupled receptors and cancer. Nat Rev Cancer 2007;7:79-94.
221. 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;116:2744-2754.
222. Kang W, Kouznetsova VL, Tsigelny IF. MiRNA in machine-learning-based diagnostics of cancers. CSP 2022;1:32-38.
223. Xu A, Kouznetsova VL, Tsigelny IF. Alzheimer’s disease diagnostics using miRNA biomarkers and machine learning. J Alzheimers Dis 2022;86:841-859.
224. Li S, Kouznetsova VL, Kesari S, Tsigelny IF. piRNA in machine-learning-based diagnostics of colorectal cancer. Molecules 2024;29.
225. Cheng Y, Wang Q, Jiang W, Bian Y, Zhou Y, Gou A, et al. Emerging roles of piRNAs in cancer: Challenges and prospects. Aging (Albany N Y) 2019;11:9932-9946.
226. Zhao AR, Kouznetsova VL, Kesari S, Tsigelny IF. Machine-learning diagnostics of breast cancer using piRNA biomarkers. Biomarkers 2025;30:167-177.