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PIWI proteins and piRNAs in cervical cancer: a propitious dart in cancer stem cell-targeted therapy

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Abstract

Any form of cancer is a result of uncontrolled cell growth caused by mutations and/or epigenetic alterations, implying that a balance of chromatin remodeling activities and epigenetic regulators is crucial to prevent the transformation of a normal cell to a cancer cell. Many of the chromatin remodelers do not recognize any specific sites on their targets and require guiding molecules to reach the respective targets. PIWI proteins and their interacting small non-coding RNAs (piRNAs) have proved to act as a guiding signal for such molecules. While epigenetic alterations lead to tumorigenesis, the stemness of cancer cells contributes to recurrence and metastasis of cancer. Various studies have propounded that the PIWI–piRNA complex also promotes stemness of cancer cells, providing new doors for target-mediated anti-cancer therapies. Despite the progress in diagnosis and development of vaccines, cervical cancer remains to be the second most prevalent cancer among women, due to the lack of cost-effective and accessible diagnostic and prevention methods. With the emergence of liquid biopsy, there is a significant demand for the ideal biomarker in the diagnosis of cancer. PIWI and piRNAs have been recommended to serve as prognostic and diagnostic markers, to differentiate early and later stages of cancer, including cervical cancer. This review discusses how PIWIs and piRNAs are involved in disease progression as well as their potential role in diagnostics and therapeutics in cervical cancer.

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References

  1. Brisson M, Kim JJJ, Canfell K, Drolet M, Gingras G, Burger EAA, et al. Impact of HPV vaccination and cervical screening on cervical cancer elimination: a comparative modelling analysis in 78 low-income and lower-middle-income countries. Lancet. 2020;395:575–90.

    Article  PubMed  PubMed Central  Google Scholar 

  2. World Health Organization. Human papillomavirus (HPV) and cervical cancer. 2019 [cited 2020 Jul 30]. Available from: https://www.who.int/health-topics/cervical-cancer#tab=tab_1.

  3. American Cancer Society. About Cervical Cancer. Available from: https://www.cancer.org/about-us/online-help/contact-us.html.

  4. Feng D, Yan K, Zhou Y, Liang H, Liang J, Zhao W, et al. PIWIl2 is reactivated by HPV oncoproteins and initiates cell reprogramming via epigenetic regulation during cervical cancer tumorigenesis. Oncol Rep. 2016;7:64575–88.

    Google Scholar 

  5. Small W, Bacon MA, Bajaj A, Chuang LT, Fisher BJ, Harkenrider MM, et al. Cervical cancer: a global health crisis. Cancer. 2017;123:2404–12.

    Article  PubMed  Google Scholar 

  6. Koutsky LA, Galloway DAHKK. Epidemiology of genital human papillomavirus infection. Epidemiol Rev. 1988;10:122–63.

    Article  CAS  PubMed  Google Scholar 

  7. Chan CK, Aimagambetova G, Ukybassova T, Kongrtay K, Azizan A. Human Papillomavirus infection and cervical cancer: epidemiology, screening, and vaccination - review of current perspectives. J Oncol. 2019;2019:1–11.

    Article  CAS  Google Scholar 

  8. Al Khudairi H, Abu-Zaid A, Alomar O, Salem H. public awareness and knowledge of pap smear as a screening test for cervical cancer among Saudi population in Riyadh city. Cureus. 2017;9:1–8.

    Google Scholar 

  9. Nour NMM. Cervical cancer: a preventable death. Rev Obstet Gynecol. 2009;2:240–4.

    PubMed  PubMed Central  Google Scholar 

  10. Manji M. Cervical cancer screening program in Saudi Arabia: Action is overdue. Ann Saudi Med. 2000;20:355–7.

    Article  CAS  PubMed  Google Scholar 

  11. Sudhalkar N, Rathod NPP, Mathews A, Chopra S, Sriram H, Shrivastava SKK, et al. Potential role of cancer stem cells as biomarkers and therapeutic targets in cervical cancer. Cancer Rep. 2019;2:e1144.

    Article  Google Scholar 

  12. Zhou BBS, Zhang H, Damelin M, Geles KG, Grindley JC, Dirks PB. Tumour-initiating cells: Challenges and opportunities for anticancer drug discovery. Nat Rev Drug Discov. 2009;8:806–23.

    Article  CAS  PubMed  Google Scholar 

  13. Mahipal V, Suraneni MDB, Suraneni MV, Badeaux MD, Mahipal V, Suraneni MDB. Tumor-initiating cells, cancer metastasis and therapeutic implications. Jandial R, editor. Madame Curie Biosci. Database. Austin (TX): Landes Bioscience; 2013 [cited 2020 Sep 22].

  14. Paldino E, Tesori V, Casalbore P, Gasbarrini A, Puglisi MA. Tumor initiating cells and chemoresistance: Which is the best strategy to target colon cancer stem cells? Biomed Res Int. 2014;2014:859871.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Khandekar D, Amara S, Tiriveedhi V. Immunogenicity of tumor initiating stem cells: Potential applications in novel anticancer therapy. Front Oncol. 2019;9:1–10.

    Article  Google Scholar 

  16. 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 Mol Cancer. 2019;18:1–15.

    PubMed  Google Scholar 

  17. Cox DNN, Chao A, Baker J, Chang L, Qiao D, Lin H. A novel class of evolutionarily conserved genes defined by PIWI are essential for stem cell self-renewal. Genes Dev. 1998;12:3715–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Litwin M, Szczepańska-Buda A, Piotrowska A, Dzięgiel P, Witkiewicz W. The meaning of PIWI proteins in cancer development (Review). Oncol Lett . 2017;13:3354–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Cox DNN, Chao A, Lin H. PIWI encodes a nucleoplasmic factor whose activity modulates the number and division rate of germline stem cells. Development. 2000;127:503–14.

    Article  CAS  PubMed  Google Scholar 

  21. Brennecke J, Aravin AAA, Stark A, Dus M, Kellis M, Sachidanandam R, et al. Discrete small RNA-generating loci as master regulators of transposon activity in drosophila. Cell. 2007;128:1089–103.

    Article  CAS  PubMed  Google Scholar 

  22. Yuan S, Tang C, Schuster A, Zhang Y, Zheng H, Yan W. Paternal pachytene piRNAs are not required for fertilization, embryonic development and sperm-mediated epigenetic inheritance in mice. Environ Epigenet. 2016;2:dvw021.

  23. Kowalczykiewicz D, Pawlak P, Lechniak D, Wrzesinski J. Altered Expression of Porcine PIWI Genes and piRNA during Development. PLoS One. 2012. https://doi.org/10.1371/journal.pone.0043816.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Deng W, Lin H. miwi, a murine homolog of PIWI, encodes a cytoplasmic protein essential for spermatogenesis. Dev Cell. 2002;2:819–30.

    Article  CAS  PubMed  Google Scholar 

  25. Grimson A, Srivastava M, Fahey B, Woodcroft BJJ, Chiang HRR, King N, et al. Early origins and evolution of microRNAs and PIWI-interacting RNAs in animals. Nature. 2008;455:1193–7.

    Article  CAS  PubMed  Google Scholar 

  26. Mei Y, Clark D, Mao L. Novel dimensions of piRNAs in cancer. Cancer Lett . 2013;336:46–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Liu X, Sun Y, Guo J, Ma H, Li J, Dong B, et al. Expression of hiwi gene in human gastric cancer was associated with proliferation of cancer cells. Int J Cancer. 2006;118:1922–9.

    Article  CAS  PubMed  Google Scholar 

  28. Kwon C, Tak H, Rho M, Chang HR, Kim YH, Kim KT, et al. Detection of PIWI and piRNAs in the mitochondria of mammalian cancer cells. Biochem Biophys Res Commun. 2014;446:218–23.

    Article  CAS  PubMed  Google Scholar 

  29. Liu JJJ, Shen R, Chen L, Ye Y, He G, Hua K, et al. PIWIl2 is expressed in various stages of breast cancers and has the potential to be used as a novel biomarker. Int J Clin Exp Pathol. 2010;3:328–37.

    PubMed  PubMed Central  Google Scholar 

  30. Gunawardane LSS, Saito K, Nishida KMM, Miyoshi K, Kawamura Y, Nagami T, et al. A slicer-mediated mechanism for repeat-associated siRNA 5’ end formation in Drosophila. Science (80-). 2007;315:1587 LP – 90.

    Article  CAS  Google Scholar 

  31. Saito K. The epigenetic regulation of transposable elements by PIWI-interacting RNAs in Drosophila. Genes Genet Syst. 2013;88:9–17.

    Article  CAS  PubMed  Google Scholar 

  32. Thomson T, Lin H. The biogenesis and function of PIWI proteins and piRNAs: progress and prospect. Annu Rev Cell Dev Biol. 2009;25:355–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Wang G, Reinke VAC. elegans PIWI, PRG-1, regulates 21U-RNAs during spermatogenesis. Curr Biol. 2008;18:861–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. 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.

    Article  CAS  PubMed  Google Scholar 

  35. Houwing S, Berezikov E, Ketting RFF. Zili is required for germ cell differentiation and meiosis in zebrafish. EMBO J. 2008;27:2702–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Tolia NHH, Joshua-Tor L. Slicer and the argonautes. Nat Chem Biol. 2007;3:36–43.

    Article  CAS  PubMed  Google Scholar 

  37. Iwasaki YW, Siomi MC, Siomi H. PIWI-interacting RNA: Its biogenesis and functions. Annu Rev Biochem . 2015;84:405–33.

    Article  CAS  PubMed  Google Scholar 

  38. Ozata DM, Gainetdinov I, Zoch A, O’Carroll D, Zamore PD. PIWI-interacting RNAs: small RNAs with big functions. Nat Rev Genet. 2019;20:89–108.

    Article  CAS  PubMed  Google Scholar 

  39. Ji L, Chen X. Regulation of small RNA stability: Methylation and beyond. Cell Res . 2012;22:624–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Zuo L, Wang Z, Tan Y, Chen X, Luo X. piRNAs and their functions in the brain. Int J Hum Genet . 2016;16:53–60.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Krishnan P, Damaraju S. piRNAs in the pathophysiology of disease and potential clinical applications. Mallick BBT-A-DN-CRna, editor. AGO-Driven Non-Coding RNAs. Elsevier Inc.; 2019.

  42. Czech B, Hannon GJ. One loop to rule them all: the ping-pong cycle and piRNA-guided silencing. Trends Biochem Sci . 2016;41:324–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. 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;1871:160–9.

    Article  CAS  PubMed  Google Scholar 

  44. Yu Y, Xiao J, Hann SS. The emerging roles of PIWI-interacting RNA in human cancers. Cancer Manag Res. 2019;11:5895–909.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Colin D, Malone GJH, Malone CD, Hannon GJ, Colin D. Malone GJH. Small RNAs as guardians of the genome. Cell. 2009;136:656-68.

    Article  CAS  Google Scholar 

  46. Keam SP, Young PE, McCorkindale AL, Dang THY, Clancy JL, Humphreys DT, et al. The human PIWI protein Hiwi2 associates with tRNA-derived piRNAs in somatic cells. Nucleic Acids Res. 2014;42:8984–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. La GA, Scarafía MA, Cañás MCH, Pérez N, Castañeda S, Colli C, et al. PIWI-interacting RNAs are differentially expressed during cardiac differentiation of human pluripotent stem cells. PLoS One. 2020;15:1–21.

    CAS  Google Scholar 

  48. Vella S, Gallo A, Antonio LN, Daniele G, Giuseppe Maria R, Michele P, et al. PIWI-interacting RNA (piRNA) signatures in human cardiac progenitor cells. Int J Biochem Cell Biol. 2016;76:1–11.

    Article  CAS  PubMed  Google Scholar 

  49. Martinez VD, Vucic EA, Thu KL, Hubaux R, Enfield KSS, Pikor LA, et al. Unique somatic and malignant expression patterns implicate PIWI-interacting RNAs in cancer-type specific biology. Sci Rep Nature . 2015;5:1–17.

    CAS  Google Scholar 

  50. Wang S, Wang Z, Tao R, He G, Liu J, Li C, 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;39:129–35.

    Article  CAS  PubMed  Google Scholar 

  51. Jain G, Stuendl A, Rao P, Berulava T, Pena Centeno T, Kaurani L, et al. A combined miRNA–piRNA signature to detect Alzheimer’s disease. Transl Psychiatry. 2019;9:250.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Stuwe E, Tóth KF, Aravin AA. Small but sturdy: Small RNAs in cellular memory and epigenetics. Genes Dev. 2014;28:423–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Guo B, Li D, Du L, Zhu X. piRNAs: biogenesis and their potential roles in cancer. Cancer Metastasis Rev. 2020;39:567–75.

    Article  PubMed  Google Scholar 

  54. Palmirotta R, Lovero D, Cafforio P, Felici C, Mannavola F, Pellè E, et al. Liquid biopsy of cancer: a multimodal diagnostic tool in clinical oncology. Ther Adv Med Oncol. 2018;10:1–24.

    Article  Google Scholar 

  55. Perspective A-P. The future of liquid biopsy. Nature. 2020;579:S9.

    Article  CAS  Google Scholar 

  56. Filant J, Nejad P, Paul A, Simonson B, Srinivasan S, Zhang X, et al. Isolation of Extracellular RNA from Serum/Plasma BT - Extracellular RNA: Methods and Protocols. In: Patel T, editor. New York: Springer 2018. p. 43–57.

  57. El-Mogy M, Lam B, Haj-Ahmad TA, McGowan S, Yu D, Nosal L, et al. Diversity and signature of small RNA in different bodily fluids using next generation sequencing. BMC Genom . 2018;19:1–24.

    Article  CAS  Google Scholar 

  58. 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;8:13353–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. 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;36:6419–23.

    Article  CAS  PubMed  Google Scholar 

  60. Li B, Hong J, Hong M, Wang Y, Yu T, Zang S, et al. piRNA-823 delivered by multiple myeloma-derived extracellular vesicles promoted tumorigenesis through re-educating endothelial cells in the tumor environment. Oncogene. 2019;38:5227–38.

    Article  CAS  PubMed  Google Scholar 

  61. Vychytilova-Faltejskova P, Stitkovcova K, Radova L, Sachlova M, Kosarova Z, Slaba K, et al. Circulating PIWI-interacting RNAs piR-5937 and piR-28876 are promising diagnostic biomarkers of colon cancer. Cancer Epidemiol Biomarkers Prev. 2018;27:1019–28.

    Article  CAS  PubMed  Google Scholar 

  62. Qiao D, Zeeman AM, Deng W, Looijenga LHL. Lin H Molecular characterization of hiwi, a human member of the PIWI gene family whose overexpression is correlated to seminomas. Oncogene. 2002;21:3988–99.

    Article  CAS  PubMed  Google Scholar 

  63. Janic A, Mendizabal L, Llamazares S, Rossell D, Gonzalez C. Ectopic expression of germline genes drives malignant brain tumor growth in Drosophila. Science (80-). 2010;330:1824.

    Article  CAS  Google Scholar 

  64. Sun G, Wang Y, Sun L, Luo H, Liu N, Fu Z, et al. Clinical significance of Hiwi gene expression in gliomas. Brain Res. 2011;1373:183–8.

    Article  CAS  PubMed  Google Scholar 

  65. Liu WKK, Jiang XYY, Zhang ZXX. Expression of PSCA, PIWIL1 and TBX2 and its correlation with HPV16 infection in formalin-fixed, paraffin-embedded cervical squamous cell carcinoma specimens. Arch Virol. 2010;155:657–63.

    Article  CAS  PubMed  Google Scholar 

  66. Liu W, Gao Q, Chen K, Xue X, Li M, Chen Q, et al. Hiwi facilitates chemoresistance as a cancer stem cell marker in cervical cancer. Oncol Rep. 2014;32:1853–60.

    Article  CAS  PubMed  Google Scholar 

  67. Li C, Zhou X, Chen J, Lu Y, Sun Q, Tao D, et al. PIWIL1 destabilizes microtubule by suppressing phosphorylation at Ser16 and RLIM-mediated degradation of stathmin1. Oncotarget. 2015;6:27794–804.

    Article  PubMed  PubMed Central  Google Scholar 

  68. 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;47:315–24.

    Article  CAS  PubMed  Google Scholar 

  69. Pei G, Li B, Ma A. Suppression of Hiwi inhibits the growth and epithelial-mesenchymal transition of cervical cancer cells. Oncol Lett . 2018;16:3874–80.

    PubMed  PubMed Central  Google Scholar 

  70. Feng D, Peng C, Li C, Zhou Y, Li M, Ling B, et al. Identification and characterization of cancer stem-like cells from primary carcinoma of the cervix uteri. Oncol Rep. 2009;22:1129–34.

    CAS  PubMed  Google Scholar 

  71. He Gang, Chen Li, Ye Yin, Xiao Yi, Hua Keding, Jarjoura David, Nakano Toru. Sanford H Barsky, Rulong Shen J-XGG PIWIl2 expressed in various stages of cervical neoplasia is a potential complementary marker for p16INK4a. Am J Transl Res. 2010;2:156–69.

    PubMed  PubMed Central  Google Scholar 

  72. Yao Y, Li C, Zhou X, Zhang Y, Lu Y, Chen J, et al. PIWIL2 induces c-Myc expression by interacting with NME2 and regulates c-Myc-mediated tumor cell proliferation. Oncol Rep. 2014;5:8466–77.

    Google Scholar 

  73. Lu Y, Zhang K, Li C, Yao Y, Tao D, Liu Y, et al. PIWIl2 suppresses P53 by inducing phosphorylation of signal transducer and activator of transcription 3 in tumor cells. PLoS One. 2012;7: e30999.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Ling W, Zhigang H, Tian H, Bin Z, Xiaolin X, Hongxiu Z. HPV 16 infection up-regulates PIWIl2, which affects cell proliferation and invasion in cervical cancer by regulating MMP-9 via the MAPK pathway. Eur J Gynaecol Oncol. 2015;36:647–54.

    CAS  PubMed  Google Scholar 

  75. Dingqing Feng, Keqin Yan, Xiao Zhang. The role of PIWIl2 in regulating the malignant process of cervical cancer. China Oncol. 2017;27:921–7.

    Google Scholar 

  76. Ye Y, Yin DTT, Chen L, Zhou Q, Shen R, He G, et al. Identification of PIWIl2-like (PL2L) proteins that promote tumorigenesis. PLoS One. 2010;5: e13406.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. Su C, Ren ZJ, Wang F, Liu M, Li X, Tang H. PIWIL4 regulates cervical cancer cell line growth and is involved in down-regulating the expression of p14ARF and p53. FEBS Lett. 2012;586:1356–62.

    Article  CAS  PubMed  Google Scholar 

  78. Lu Y, Li C, Zhang K, Sun H, Tao D, Liu Y, et al. Identification of piRNAs in Hela cells by massive parallel sequencing. BMB Rep. 2010;43:635–41.

    Article  CAS  PubMed  Google Scholar 

  79. 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;412:1621–5.

    Article  CAS  PubMed  Google Scholar 

  80. Yang T, Rycaj K. Targeted therapy against cancer stem cells (review). Oncol Lett. 2015;10:27–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Qureshi-Baig K, Ullmann P, Haan S, Letellier E. Tumor-Initiating Cells: A criTICal review of isolation approaches and new challenges in targeting strategies. Mol Cancer . 2017;16:1–16.

    Article  CAS  Google Scholar 

  82. Shibata M, Hoque MO. Targeting cancer stem cells: A strategy for effective eradication of cancer. Cancers (Basel). 2019;11:732.

    Article  CAS  Google Scholar 

  83. Fathizadeh H, Asemi Z. Epigenetic roles of PIWI proteins and piRNAs in lung cancer. Cell Biosci . 2019;9:1–8.

    Article  CAS  Google Scholar 

  84. Siddiqi S, Matushansky I. PIWIs and PIWI-interacting RNAs in the epigenetics of cancer. J Cell Biochem. 2012;113:373–80.

    Article  CAS  PubMed  Google Scholar 

  85. Watanabe T, Lin H. Posttranscriptional regulation of gene expression by PIWI proteins and piRNAs. Mol Cell. 2014;56:18–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. 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.

    Article  CAS  PubMed  Google Scholar 

  87. Ai L, Mu S, Sun C, Fan F, Yan H, Qin Y, et al. Myeloid-derived suppressor cells endow stem-like qualities to multiple myeloma cells by inducing piRNA-823 expression and DNMT3B activation. Mol Cancer. 2019;18:1–12.

    Article  Google Scholar 

  88. Wang Q-E, Han C, Milum K, Wani AAA. Stem cell protein PIWIl2 modulates chromatin modifications upon cisplatin treatment. Mutat Res Mol Mech Mutagen. 2011;708:59–68.

    Article  CAS  Google Scholar 

  89. Wang Y, Gable T, Ma MZZ, Clark D, Zhao J, Zhang Y, et al. A piRNA-like small RNA induces chemoresistance to cisplatin-based therapy by inhibiting apoptosis in lung squamous cell carcinoma. Mol Ther Nucleic acids. 2017;6:269–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Wang X, Sun S, Tong X, Ma Q, Di H, Fu T, et al. MiRNA-154-5p inhibits cell proliferation and metastasis by targeting PIWIL1 in glioblastoma. Brain Res. 2017;1676:69–76.

    Article  CAS  PubMed  Google Scholar 

  91. Lee YJYS, Moon SU, Park MG, Jung WY, Park YK, Song SK, et al. Multiplex bioimaging of piRNA molecular pathway-regulated theragnostic effects in a single breast cancer cell using a piRNA molecular beacon. Biomaterials. 2016;101:143–55.

    Article  CAS  PubMed  Google Scholar 

  92. Cheng J, Deng H, Xiao B, Zhou H, Zhou F, Shen Z, et al. PiR-823, a novel non-coding small RNA, demonstrates in vitro and in vivo tumor suppressive activity in human gastric cancer cells. Cancer Lett. 2012;315:12–7.

    Article  CAS  PubMed  Google Scholar 

  93. Tan L, Mai D, Zhang B, Jiang X, Zhang J, Bai R, et al. PIWI-interacting RNA-36712 restrains breast cancer progression and chemoresistance by interaction with SEPW1 pseudogene SEPW1P RNA. Mol Cancer . 2019;18:1–15.

    Article  Google Scholar 

  94. Jacobs DI, Qin Q, Fu A, Chen Z, Zhou J, Zhu Y. piRNA-8041 is downregulated in human glioblastoma and suppresses tumor growth in vitro and in vivo. Oncotarget. 2018;9:37616–26.

    Article  PubMed  PubMed Central  Google Scholar 

  95. Assumpção CB, Calcagno DQ, Araújo TMT, Batista Dos Santos SE, Ribeiro Dos Santos ÂKC, Riggins GJ, et al. The role of piRNA and its potential clinical implications in cancer. Epigenomics. 2015;7:975–84.

  96. Han YNY-N, Li Y, Xia SQS-Q, Zhang Y-YYY, Zheng JHJ-HJH, Li W. PIWI Proteins and PIWI-Interacting RNA: Emerging Roles in Cancer. Cell Physiol Biochem. 2017;44:1–20.

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The authors would like to acknowledge Pooja S.R and Joby Issac for editing this manuscript.

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Kunnummal, M., Angelin, M. & Das, A.V. PIWI proteins and piRNAs in cervical cancer: a propitious dart in cancer stem cell-targeted therapy. Human Cell 34, 1629–1641 (2021). https://doi.org/10.1007/s13577-021-00590-4

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