Science, Technology, Engineering and Mathematics.
Open Access

CURRENT RESEARCH STATUS OF PIWI-PIRNA IN MALIGNANT TUMORS

Download as PDF

Volume 3, Issue 1, Pp 17-23, 2025

DOI: https://doi.org/10.61784/wjbs3016

Author(s)

Mi Meng1Bo Yu2*

Affiliation(s)

1Department of Thoracic Oncology, The second Affiliated Hospital of Zunyi Medical University, Zunyi, China.

2Department of Urology, The second Affiliated Hospital of Zunyi Medical University, Zunyi, China.

Corresponding Author

Bo Yu

ABSTRACT

PIWI-interacting RNA (piRNA) is a type of small non-coding RNA linked to the PIWI branch of the Argonaute family of proteins. PiRNA was initially identified in animal germline cells and is essential for germline development. Recent findings suggest that beyond reproductive functions, aberrant expression of PIWI/piRNA is strongly associated with several human cancers. The PIWI-piRNA complex in the reproductive system preserves genomic integrity by suppressing transposable elements. Recent research has also demonstrated that the PIWI-piRNA complex regulates protein-coding genes, thereby impacting the development and progression of human tumors. With further insights into piRNA biology, it has become clear that in addition to directly cleaving and degrading target RNA akin to the Ago/miRNA family, PIWI proteins/piRNA can regulate human cancers through epigenetic factors, such as DNA methylation and RNA methylation. In this article, we provide an overview of the molecular mechanisms underlying piRNA biogenesis and the latest functional insights into piRNA's role in human cancers, along with recent research advancements.

KEYWORDS

ncRNA (Non-coding RNA); Piwi-interacting RNA (piRNA); Malignant neoplasms; Biological marker

CITE THIS PAPER

Mi Meng, Bo Yu. Current research status of PIWI-piRNA in malignant tumors. World Journal of Biomedical Sciences. 2025, 3(1): 17-23. DOI: https://doi.org/10.61784/wjbs3016.

REFERENCES

[1] PCAWG Transcriptome Core Group, Calabrese C, Davidson NR, et al. Genomic basis for RNA alterations in cancer. Nature, 2020, 578(7793): 129-136.

[2] Cech T R, Steitz J A. The noncoding RNA revolution-trashing old rules to forge new ones. Cell, 2014, 157(1): 77-94.

[3] Shi J, Zhou T, Chen Q. Exploring the expanding universe of small RNAs. Nat Cell Biol, 2022, 24(4): 415-423.

[4] Slack F J, Chinnaiyan A M. The Role of Non-coding RNAs in Oncology. Cell, 2019, 179(5): 1033-1055.

[5] Liu Y, Dou M, Song X, et al. The emerging role of the piRNA /piwi complex in cancer. Mol Cancer, 2019, 18(1): 123.

[6] He J, Chen M, Xu J, et al. Identification and characterization of Piwi-interacting RNAs in human placentas of preeclampsia. Sci Rep, 2021, 11(1): 15766.

[7] Iwasaki Y W, Siomi M C, Siomi Het, et al. PIWI-Interacting RNA: Its Biogenesis and Functions. Annu Rev Biochem, 2015, 84: 405-33.

[8] Saxe J P, Chen M, Zhao H, et al. Tdrkh is essential for spermatogenesis and participates in primary piRNA biogenesis in the germline. EMBO J, 2013, 32(13): 1869-1885.

[9] Anzelon T A, Chowdhury S, Hughes S M, et al. Structural basis for piRNA targeting. Nature, 2021, 597(7875): 285-289.

[10] Tang W, Tu S, Lee H C, et al. The RNase PARN-1 trims piRNA 3'ends to promote transcriptome surveillance in C. elegans. Cell, 2016, 164(5): 974-984.

[11] Izumi N, Shoji K, Sakaguchi Y, et al. Identification and functional analysis of the pre-piRNA 3' trimmer in silkworms. Cell, 2016, 164(5): 962-973.

[12] Mann J M, Wei C, Chen C, et al. How genetic defects in piRNA trimming contribute to male infertility. Andrology, 2023, 11(5): 911-917.

[13] Liu J, Chen M, Ma L, et al. piRNA-36741 regulates BMP2-mediated osteoblast differentiation via METTL3 controlled m6A modification. Aging (Albany NY), 2021, 13(19): 23361-23375.

[14] Wang X, Gou LT, Liu M F. Noncanonical functions of PIWIL1/piRNAs in animal male germ cells and human diseases. Biol Reprod, 2022, 107(1): 101-108.

[15] Nagirnaja L, Morup N, Nielsen J E, et al. Defective piRNA Processing, and Azoospermia. N Engl J Med, 2021, 385(8): 707-719.

[16] Gou L T, Kang J Y, Dai P, et al. Ubiquitination-Deficient Mutations in Human Piwi Cause Male Infertility by Impairing Histone-to-Protamine Exchange during Spermiogenesis. Cell, 2017, 169(6): 1090-1104.e13.

[17] Tan Y Q, Tu C, Meng L, et al. Loss-of-function mutations in TDRD7 lead to a rare novel syndrome combining congenital cataract and nonobstructive azoospermia in humans. Genet Med, 2019, 21(5): 1209-1217.

[18] Guan Y, Keeney S, Jain D, et al. Yama, a mutant allele of Mov10l1, disrupts retrotransposon silencing and piRNA biogenesis. PLoS Genet, 2021, 17(2): e1009265.

[19] Qureshi S, Hardy J J, Pombar C, et al. Genomic study of TEX15 variants:prevalence and allelic heterogeneity in men with spermatogenic failure. Front Genet, 2023, 14: 1134849.

[20] Babakhanzadeh E, Khodadadian A, Rostami S, et al. Testicular expression of TDRD1, TDRD5, TDRD9 and TDRD12 in azoospermia. BMC Med Genet, 2020, 21(1): 33.

[21] Roovers E F, Rosenkranz D, Mahdipour M, et al. Piwi proteins and piRNAs in mammalian oocytes and early embryos. Cell Rep, 2015, 10(12): 2069-2082.

[22] Li F, Yuan P, Rao M, et al. piRNA-independent function of PIWIL1 as a co-activator for anaphase promoting complex/cyclosome to drive pancreatic cancer metastasis. Nat Cell Biol, 2020, 22(4): 425-438.

[23] Shi S, Yang Z Z, Liu S, et al. PIWIL1 promotes gastric cancer via a piRNA-independent  mechanism, 2020, 117(36): 22390-22401.

[24] Liu J, Zhang S, Cheng B. Epigenetic roles of PIWI-interacting RNAs (piRNAs)in cancer metastasis (Review). Oncol Rep, 2018, 40(5): 2423-2434.

[25] Pammer J, Rossiter H, Bilban M, et al. PIWIL-2 and piRNAs are regularly expressed in epithelia of the skin and their expression is related to differentiation. Arch Dermatol Res, 2020, 312(10): 705-714.

[26] Mann J R, Mattiske D M. RNA interference in mammalian DNA methylation. Biochem Cell Biol, 2012, 90(1): 70-77.

[27] Liu T, Wang J, Sun L, 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(16): 1603-1616.

[28] Litwin M, Szczepańska-Buda A, Michalowska D, et al. Aberrant Expression of PIWIL1 and PIWIL2 and Their Clinical Significance in Ductal Breast Carcinoma. Anticancer Res, 2018, 38(4): 2021-2030.

[29] Fu A, Jacobs D I, Hoffman A E, et al. PIWI-interacting RNA 021285 is involved in breast tumorigenesis possibly by remodeling the cancer epigenome. Carcinogenesis, 2015, 36(10): 1094-1102.

[30] Ding X, Li Y, Lü J, et al. piRNA-823 Is Involved in Cancer Stem Cell Regulation Through Altering DNA Methylation in Association with Luminal Breast Cancer. Front Cell Dev Biol, 2021, 9: 641052.

[31] Li B, Hong J, Hong M, et al. piRNA-823 delivered bymultiple myeloma-derived extracellular vesicles promoted tumorigenesis throughre-educating endothelial cells in the tumor environment. Oncogene, 2019, 38(26): 5227-5238.

[32] Yan H, Wu Q L, Sun C Y, et al. piRNA-823 contributes to tumorigenesis by regulating de novoDNA methylation and angiogenesis in multiple myeloma. Leukemia, 2015, 29(1): 196-206.

[33] Su J F, Zhao F, Gao Z W, et al. piR-823 demonstrates tumor oncogenic activity in esophageal squamous cell carcinoma through DNA methylation induction via DNA methyltransferase 3B. Pathol Res Pract, 2020, 216(4): 152848.

[34] Nakayama M, Gonzalgo M L, Yegnasubramanian S, et al. GSTP1 CpG island hypermethylation as a molecular biomarker for prostate cancer. J Cell Biochem, 2004, 91(3): 540-552.

[35] Wu D, Fu H, Zhou H, et al. 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.

[36] Amaar Y G, Reeves M E. The impact of the RASSF1C and PIWIL1 on DNA methylation: the identification of GMIP as a tumor suppressor. Oncotarget, 2020, 11(45): 4082-4092.

[37] Sun T, Wu R, Ming L. The role of m6A RNA methylation in cancer. Biomed Pharmacother, 2019, 112: 108613.

[38] Yadav P, Subbarayalu P, Medina D, et al. M6A RNA Methylation Regulates HistoneUbiquitination to Support Cancer Growth and Progression. Cancer Res, 2022, 82(10): 1872-1889.

[39] Xie Q, Li Z, Luo X, et al. piRNA-14633 promotes cervical cancer cell malignancy in a METTL14-dependent m6A RNA methylation manner. J Transl Med, 2022, 20(1): 51.

[40] Han H, Fan G, Song S, et al. piRNA-30473 contributes to tumorigenesis and poor prognosis by regulating m6A RNA methylation in DLBCL. Blood, 2021, 137(12): 1603-1614.

[41] Gao X Q, Zhang Y H, Liu F, et al. The piRNA CHAPIR regulates cardiac hypertrophy by controlling METTL3-dependent N6-methyladenosine methylation of Parp10 mRNA. Nat Cell Biol, 2020, 22(11): 1319-1331.

[42] He X, Chen X, Zhang X, et al. An Lnc RNA (GAS5)/SnoRNA-derived piRNA induces activation of TRAIL gene by site-specifically recruitingMLL/COMPASS-like complexes. Nucleic Acids Res, 2015, 43(7): 3712-3725.

[43] Mei Y, Wang Y, Kumari P, et al. A piRNA-like small RNA interacts with and modulates p-ERM proteins in human somatic cells. Nat Commun, 2015, 6: 7316.

[44] Yin Jie, Jiang Xiao-Yu, Qi Wei, et al. piR-823 contributes to colorectal tumorigenesis by enhancing the transcriptional activity of HSF1. Cancer science, 2017, 108(9):1746-1756.

[45] Krishnan, Aswini R, Qu, Yuanhao, et al. Computational methods reveal novel functionalities of PIWI-interacting RNAs in human papillomavirus-induced head and neck squamous cell carcinoma. Oncotarget, 2017, 9(4): 4614-4624.

[46] Qian L, Xie H, Zhang L, et al. Piwi-Interacting RNAs: A New Class of Regulator in Human Breast Cancer. Front Oncol, 2021, 11: 695077.

[47] Roy J, Das B, Jain N, et al. PIWI-interacting RNA 39980 promotes tumor progression and reduces drug sensitivity in neuroblastoma cells. J Cell Physiol, 2020, 235(3): 2286-2299.

[48] Chu H, Hui G, Yuan L, et al. Identification of novel piRNAs in bladder cancer. Cancer Lett. 2015, 356(2 Pt B): 561-567.

[49] Rajan K S, Ramasamy S. Retrotransposons and piRNA: the missing link in central nervous system. Neurochem Int, 2014, 77: 94-102.

[50] Tindell S J, Rouchka E C, Arkov A L. Glial granules contain germline proteins in the Drosophila brain, which regulate brain transcriptome. Commun Biol, 2020, 3(1): 699.

[51] Salloum-Asfar S, Elsayed A K, Elhag S F, et al. Circulating Non-Coding RNAs as a Signature of Autism Spectrum Disorder Symptomatology. Int J Mol Sci, 2021, 22(12): 6549.

[52] Zhang T, Wong G. Dysregulation of Human Somatic piRNA Expression in Parkinson's Disease Subtypes and Stages. Int J Mol Sci, 2022, 23(5): 2469.

[53] Huang X, Yuan T, Tschannen M, et al. Characterization of human plasma-derived exosomal RNAs by deep sequencing. BMC Genomics, 2013, 14: 319.

[54] Yuan T, Huang X, Woodcock M, et al. Plasma extracellular RNA profiles in healthy and cancer patients. Sci Rep, 2016, 6: 19413.

[55] Bahn J H, Zhang Q, Li F, et al. The landscape of microRNA, Piwi-interacting RNA, and circular RNA in human saliva. Clin Chem, 2015, 61(1): 221-230.

[56] Hong Y, Wang C, Fu Z, et al. Systematic characterization of seminal plasma piRNAs as molecular biomarkers for male infertility. Sci Rep, 2016, 6: 24229.

[57] El-Mogy M, Lam B, Haj-Ahmad T A, et al. Diversity and signature of small RNA in different bodily fluids using next generation sequencing. BMC Genomics, 2018, 19(1): 408.

All published work is licensed under a Creative Commons Attribution 4.0 International License. sitemap
Copyright © 2017 - 2025 Science, Technology, Engineering and Mathematics.   All Rights Reserved.