Involvement of PIWI-interacting RNAs in Cancerogenesis via the Regulation of Gene Expression
Authors:
S. Rybecká; K. Štítkovcová; P. Vychytilová-Faltejsková; O. Slabý
Authors place of work:
CEITEC – Středoevropský technologický institut, MU, Brno
Published in the journal:
Klin Onkol 2016; 29(6): 428-438
Category:
Review
doi:
https://doi.org/10.14735/amko2016428
Summary
Background:
In the past few years, a number of studies have suggested that small non-coding RNAs could be promising diagnostic, prognostic and predictive biomarkers in oncology. Recently, small RNAs interacting with PIWI proteins (piRNAs) have been described. These small RNAs regulate gene expression at transcriptional and post-transcriptional levels; however, they appear to be specifically involved in silencing the transposable elements LINE and SINE and are thus considered to contribute to genomic stability. Furthermore, piRNAs participate also in other important biological processes, such as gametogenesis, chromosome segregation, and stem cell self-renewal. Although their expression was first noted in germ line cells, they are now known to be present in all tissue types and their expression is highly tissue-specific. In addition, piRNA expression is dysregulated in tumor tissues. Nevertheless, the exact function of these molecules in cancerogenesis is not known. Recently, free circulating piRNAs were reported to be stably present in body fluids, suggesting that they could serve as promising noninvasive biomarkers to enable early diagnosis, therapy response prediction, and accurate prognosis prediction of cancer patients.
Aim:
The aim of this review is to summarize current knowledge about piRNA biogenesis and their functions in the regulation of gene expression and transposons silencing. In addition, the review focuses on piRNAs that show dysregulated expression in different types of cancers and that could serve as potential diagnostic biomarkers and/or therapeutic targets.
Key words:
PIWI-interacting RNAs – piRNA – biogenesis – cancer – transposon silencing – biomarkers – therapeutic targets
The results of this research have been acquired within CEITEC 2020 (LQ1601) project with financial contribution made by the Ministry of Education, Youths and Sports of the Czech Republic within special support paid from the National Programme for Sustainability II funds.
The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.
The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.
Submitted:
23. 11. 2016
Accepted:
5. 12. 2016
Zdroje
1. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144 (5): 646–674. doi: 10.1016/j.cell. 2011.02.013.
2. Sabin LR, Delás MJ, Hannon GJ. Dogma derailed: the many influences of RNA on the genome. Mol Cell 2013; 49 (5): 783–794. doi: 10.1016/j.molcel.2013.02.010.
3. Baylin SB, Jones PA. A decade of exploring the cancer epigenome – biological and translational implications. Nat Rev Cancer 2011; 11 (10): 726–734. doi: 10.1038/nrc3130.
4. Luteijn MJ, Ketting RF. PIWI-interacting RNAs: from generation to transgenerational epigenetics. Nat Rev Genet 2013; 14 (8): 523–534. doi: 10.1038/nrg3495.
5. Sana J, Faltejskova P, Svoboda M et al. Novel classes of non-coding RNAs and cancer. J Transl Med 2012; 10: 103. doi: 10.1186/1479-5876-10-103.
6. Chinwalla AT, Cook LL, Delehaunty KD et al. Initial sequencing and comparative analysis of the mouse genome. Nature 2002; 420 (6915): 520–562.
7. Slotkin RK, Martienssen R. Transposable elements and the epigenetic regulation of the genome. Nat Rev Genet 2007; 8 (4): 272–285.
8. Goodier JL, Kazazian HH. Retrotransposons revisited: the restraint and rehabilitation of parasites. Cell 2008; 135 (1): 23–35. doi: 10.1016/j.cell.2008.09.022.
9. Lim RS, Kai T. A piece of the pi (e): the diverse roles of animal piRNAs and their PIWI partners. Semin Cell Dev Biol 2015; 47–48: 17–31. doi: 10.1016/j.semcdb.2015.10.025.
10. Höck J, Meister G. The Argonaute protein family. Genome Biol 2008; 9 (2): 210. doi: 10.1186/gb-2008-9-2-210.
11. Kim VN, Han J, Siomi MC. Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol 2009; 10 (2): 126–139. doi: 10.1038/nrm2632.
12. Parker JS, Barford D. Argonaute: a scaffold for the function of short regulatory RNAs. Trends Biochem Sci 2006; 31 (11): 622–630.
13. Zhai L, Wang L, Teng F et al. Argonaute and argonaute-bound small RNAs in stem cells. Int J Mol Sci 2016; 17 (2): 208. doi: 10.3390/ijms17020208.
14. Ku HY, Lin H. PIWI proteins and their interactors in piRNA biogenesis, germline development and gene expression. Natl Sci Rev 2014; 1 (2): 205–218.
15. Aravin A, Gaidatzis D, Pfeffer S et al. A novel class of small RNAs bind to MILI protein in mouse testes. Nature 2006; 442 (7099): 203–207.
16. Girard A, Sachidanandam R, Hannon GJ et al. A germline-specific class of small RNAs binds mammalian Piwi proteins. Nature 2006; 442 (7099): 199–202.
17. Pane A, Wehr K, Schüpbach T. Zucchini and squash encode two putative nucleases required for rasiRNA production in the Drosophila germline. Dev Cell 2007; 12 (6): 851–862.
18. Rengaraj D, Lee S, Park T et al. Small non-coding RNA profiling and the role of piRNA pathway genes in the protection of chicken primordial germ cells. BMC Genomics 2014; 15: 757. doi: 10.1186/1471-2164-15-757.
19. Aravin AA, Sachidanandam R, Bourc’his D et al. A piRNA pathway primed by individual transposons is linked to de novo DNA methylation in mice. Mol Cell 2008; 31 (6): 785–799. doi: 10.1016/j.molcel.2008.09.003.
20. Kuramochi-Miyagawa S, Watanabe T, Gotoh K et al. DNA methylation of retrotransposon genes is regulated by Piwi family members MILI and MIWI2 in murine fetal testes. Genes Dev 2008; 22 (7): 908–917. doi: 10.1101/gad.1640708.
21. Pezic D, Manakov SA, Sachidanandam R et al. piRNA pathway targets active LINE1 elements to establish the repressive H3K9me3 mark in germ cells. Genes Dev 2014; 28 (13): 1410–1428. doi: 10.1101/gad.240895.114.
22. Rajasethupathy P, Antonov I, Sheridan R et al. A role for neuronal piRNAs in the epigenetic control of memory-related synaptic plasticity. Cell 2012; 149 (3): 693–707. doi: 10.1016/j.cell.2012.02.057.
23. Lee EJ, Banerjee S, Zhou H et al. Identification of piRNAs in the central nervous system. RNA 2011; 17 (6): 1090–1099. doi: 10.1261/rna.2565011.
24. Yan Z, Hu HY, Jiang X et al. Widespread expression of piRNA-like molecules in somatic tissues. Nucleic Acids Res 2011; 39 (15): 6596–6607. doi: 10.1093/nar/gkr298.
25. Houwing S, Kamminga LM, Berezikov E et al. A role for Piwi and piRNAs in germ cell maintenance and transposon silencing in Zebrafish. Cell 2007; 129 (1): 69–82.
26. Khurana JS, Theurkauf W. piRNAs, transposon silencing, and Drosophila germline development. J Cell Biol 2010; 191 (5): 905–913. doi: 10.1083/jcb.201006034.
27. Brennecke J, Aravin AA, Stark A et al. Discrete small RNA-generating loci as master regulators of transposon activity in Drosophila. Cell 2007; 128 (6): 1089–1103.
28. Goh WS, Seah JW, Harrison EJ et al. A genome-wide RNAi screen identifies factors required for distinct stages of C. elegans piRNA biogenesis. Genes Dev 2014; 28 (7): 797–807. doi: 10.1101/gad.235622.113.
29. Khurana JS, Theurkauf W. piRNAs, transposon silencing, and Drosophila germline development. J Cell Biol 2010; 191 (5): 905–913. doi: 10.1083/jcb.201006034.
30. 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 (21): 2361–2373. doi: 10.1101/gad.203786.112.
31. 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. doi: 10.1016/j.tibs.2015.12.008.
32. Luteijn MJ, Ketting RF. PIWI-interacting RNAs: from generation to transgenerational epigenetics. Nat Rev Genet 2013; 14 (8): 523–534. doi: 10.1038/nrg3495.
33. Ketting RF. The many faces of RNAi. Dev Cell 2011; 20 (2): 148–161. doi: 10.1016/j.devcel.2011.01.012.
34. Guzzardo PM, Muerdter F, Hannon GJ. The piRNA pathway in flies: highlights and future directions. Curr Opin Genet Dev 2013; 23 (1): 44–52. doi: 10.1016/j.gde.2012.12.003.
35. Siomi MC, Sato K, Pezic D et al. PIWI-interacting small RNAs: the vanguard of genome defence. Nat Rev Mol Cell Bio 2011; 12 (4): 246–258. doi: 10.1038/nrm3089.
36. Kuramochi-Miyagawa S, Kimura T, Yomogida K et al. Two mouse piwi-related genes: miwi and mili. Mech Dev 2001; 108 (1–2): 121–133.
37. Reuter M, Chuma S, Tanaka T et al. Loss of the Mili-interacting tudor domain-containing protein-1 activates transposons and alters the Mili-associated small RNA profile. Nat Struct Mol Biol 2009; 16 (6): 639–646. doi: 10.1038/nsmb.1615.
38. Sienski G, Dönertas D, Brennecke J. Transcriptional silencing of transposons by Piwi and maelstrom and its impact on chromatin state and gene expression. Cell 2012; 151 (5): 964–980. doi: 10.1016/j.cell.2012.10.040.
39. Le Thomas A, Rogers AK, Webster A et al. Piwi induces piRNA-guided transcriptional silencing and establishment of a repressive chromatin state. Genes Dev 2013; 27 (4): 390–399. doi: 10.1101/gad.209841.112.
40. Bagijn MP, Goldstein LD, Sapetschnig A et al. Function, targets, and evolution of caenorhabditis elegans piRNAs. Science 2012; 337 (6094): 574–578. doi: 10.1126/science.1220952.
41. Ashe A, Sapetschnig A, Weick EM et al. piRNAs can trigger a multigenerational epigenetic memory in the germline of C. elegans. Cell 2012; 150 (1): 88–99. doi: 10.1016/j.cell.2012.06.018.
42. Shirayama M, Seth M, Lee HC et al. piRNAs initiate an epigenetic memory of nonself RNA in the C. elegans germline. Cell 2012; 150 (1): 65–77. doi: 10.1016/j.cell. 2012.06.015.
43. Faulkner GJ, Kimura Y, Daub CO et al. The regulated retrotransposon transcriptome of mammalian cells. Nat Genet 2009; 41 (5): 563–571. doi: 10.1038/ng.368.
44. Lim AK, Lorthongpanich C, Chew TG et al. The nuage mediates retrotransposon silencing in mouse primordial ovarian follicles. Development 2013; 140 (18): 3819–3825. doi: 10.1242/dev.099184.
45. Watanabe T, Lin H. Posttranscriptional regulation of gene expression by Piwi proteins and piRNAs. Mol Cell 2014; 56 (1): 18–27. doi: 10.1016/j.molcel.2014.09.012.
46. Kotelnikov RN, Klenov MS, Rozovsky YM et al. Peculiarities of piRNA-mediated post-transcriptional silencing of Stellate repeats in testes of Drosophila melanogaster. Nucleic Acids Res 2009; 37 (10): 3254–3263. doi: 10.1093/nar/gkp167.
47. Kiuchi T, Koga H, Kawamoto M et al. A single female-specific piRNA is the primary determiner of sex in the silkworm. Nature 2014; 509 (7502): 633–636. doi: 10.1038/nature13315.
48. Shpiz S, Ryazansky S, Olovnikov I et al. Euchromatic transposon insertions trigger production of novel Pi- and Endo-siRNAs at the target sites in the drosophila germline. PLoS Genet 2014; 10 (2): e1004138. doi: 10.1371/journal.pgen.1004138.
49. Qiao D, Zeeman AM, Deng W et al. Molecular characterization of hiwi, a human member of the piwi gene family whose overexpression is correlated to seminomas. Oncogene 2002; 21 (25): 3988–3999.
50. Suzuki R, Honda S, Kirino Y. PIWI expression and function in cancer. Front Genet 2012; 3: 204. doi: 10.3389/fgene.2012.00204.
51. Sun G, Wang Y, Sun L et al. Clinical significance of Hiwi gene expression in gliomas. Brain Res 2011; 1373: 183–188. doi: 10.1016/j.brainres.2010.11.097.
52. Wang Y, Liu Y, Shen X et al. The PIWI protein acts as a predictive marker for human gastric cancer. Int J Clin Exp Pathol 2012; 5 (4): 315–325.
53. Saito K, Nishida KM, Mori T et al. Specific association of Piwi with rasiRNAs derived from retrotransposon and heterochromatic regions in the Drosophila genome. Genes Dev 2006; 20 (16): 2214–2222.
54. Cox DN, Chao A, Baker J et al. A novel class of evolutionarily conserved genes defined by piwi are essential for stem cell self-renewal. Genes Dev 1998; 12 (23): 3715–3727.
55. Grimaud C, Bantignies F, Pal-Bhadra M et al. RNAi components are required for nuclear clustering of Polycomb group response elements. Cell 2006; 124 (5): 957–971.
56. Yin H, Lin H. An epigenetic activation role of Piwi and a Piwi-associated piRNA in Drosophila melanogaster. Nature 2007; 450 (7167): 304–308.
57. Siddiqi S, Matushansky I. Piwis and piwi-interacting RNAs in the epigenetics of cancer. J Cell Biochem 2012; 113 (2): 373–380. doi: 10.1002/jcb.23363.
58. Esteller M. Non-coding RNAs in human disease. Nat Rev Genet 2011; 12 (12): 861–874. doi: 10.1038/nrg3074.
59. Cheng J, Deng H, Xiao B et al. piR-823, a novel non-coding small RNA, demonstrates in vitro and in vivo tumor suppressive activity in human gastric cancer cells. Cancer Lett 2012; 315 (1): 12–17. doi: 10.1016/j.canlet.2011.10.004.
60. Iliev R, Stanik M, Fedorko M et al. Decreased expression levels of PIWIL1, PIWIL2, and PIWIL4 are associated with worse survival in renal cell carcinoma patients. Oncotargets Ther 2016; 9: 217–222. doi: 10.2147/OTT.S91 295.
61. Iliev R, Fedorko M, Machackova T et al. Expression levels of PIWI-interacting RNA piR-823 are deregulated in tumor tissue blood serum and urine of patients with renal cell carcinoma. Anticancer Res 2016; 36 (12): 6419–6423.
62. Yan H, Wu QL, Sun CY et al. piRNA-823 contributes to tumorigenesis by regulating de novo DNA methylation and angiogenesis in multiple myeloma. Leukemia 2015; 29 (1): 196–206. doi: 10.1038/leu.2014.135.
63. Cuiyun Y, Ning Q, Li ZP et al. Non-coding RNAs: new therapeutic targets and opportunities for hepatocellular carcinoma. Adv Mod Oncol Res 2016; 2 (1): 5–17.
64. Cheng J, Guo JM, Xiao BX et al. piRNA, the new non-coding RNA, is aberrantly expressed in human cancer cells. Clin Chim Acta 2011; 412 (17–18): 1621–1625. doi: 10.1016/j.cca.2011.05.015.
65. Chu H, Hui G, Yuan L et al. Identification of novel piRNAs in bladder cancer. Cancer Lett 2015; 356 (2): 561–567. doi: 10.1016/j.canlet.2014.10.004.
66. Huang G, Hu H, Xue X et al. Altered expression of piRNAs and their relation with clinicopathologic features of breast cancer. Clin Transl Oncol 2013; 15 (7): 563–568. doi: 10.1007/s12094-012-0966-0.
67. Hashim A, Rizzo F, Marchese G et al. RNA sequencing identifies specific PIWI-interacting small non-coding RNA expression patterns in breast cancer. Oncotarget 2014; 5 (20): 9901–9910.
68. Martinez VD, Enfield KS, Rowbotham DA et al. An atlas of gastric PIWI-interacting RNA transcriptomes and their utility for identifying signatures of gastric cancer recurrence. Gastric Cancer 2016; 19 (2): 660–665. doi: 10.1007/s10120-015-0487-y.
69. Kishikawa T, Otsuka M, Ohno M et al. Circulating RNAs as new biomarkers for detecting pancreatic cancer. World J Gastroenterol 2015; 21 (28): 8527–8540. doi: 10.3748/wjg.v21.i28.8527.
70. Yang X, Cheng Y, Lu Q et al. Detection of stably expressed piRNAs in human blood. Int J Clin Exp Med 2015; 8 (8): 13353–13358.
71. Bahn JH, Zhang Q, Li F et al. The landscape of microRNA, Piwi-interacting RNA, and circular RNA in human saliva. Clin Chem 2015; 61 (1): 221–230. doi: 10.1373/clinchem.2014.230433.
72. Cui L, Lou Y, Zhang X et al. Detection of circulating tumor cells in peripheral blood from patients with gastric cancer using piRNAs as markers. Clin Biochem 2011; 44 (13): 1050–1057. doi: 10.1016/j.clinbiochem.2011.06.004.
73. Zhou H, Guo JM, Lou YR et al. Detection of circulating tumor cells in peripheral blood from patients with gastric cancer using microRNA as a marker. J Mol Med 2010; 88 (7): 709–717. doi: 10.1007/s00109-010-0617-2.
74. Li PF. Non-coding RNAs and gastric cancer. World J Gastroenterol 2014; 20 (18): 5411–5419. doi: 10.3748/wjg.v20.i18.5411.
75. Assumpção CB, Calcagno DQ, Araújo TM et al. The role of piRNA and its potential clinical implications in cancer. Epigenomics 2015; 7 (6): 975–984. doi: 10.2217/epi.15.37.
76. Mei Y, Clark D, Mao L. Novel dimensions of piRNAs in cancer. Cancer Lett 2013; 336 (1): 46–52. doi: 10.1016/j.canlet.2013.04.008.
77. Martinez VD, Vucic EA, Thu KL et al. Unique somatic and malignant expression patterns implicate PIWI-interacting RNAs in cancer-type specific biology. Sci Rep 2015; 5: 10423. doi: 10.1038/srep10423.
78. Müller S, Raulefs S, Bruns P et al. Next-generation sequencing reveals novel differentially regulated mRNAs, lncRNAs, miRNAs, sdRNAs and a piRNA in pancreatic cancer. Mol Cancer 2015; 14 (1): 94. doi: 10.1186/s12943-015-0358-5.
79. Mei YP, Liao JP, Shen J et al. Small nucleolar RNA 42 acts as an oncogene in lung tumorigenesis. Oncogene 2012; 31 (22): 2794–2804. doi: 10.1038/onc.2011.449.
80. Busch J, Ralla B, Jung M et al. Piwi-interacting RNAs as novel prognostic markers in clear cell renal cell carcinomas. J Exp Clin Cancer Res 2015; 34 (1): 61. doi: 10.1186/s13046-015-0180-3.
81. Li Y, Wu X, Gao H et al. Piwi-interacting RNAs (piRNAs) are dysregulated in renal cell carcinoma and associated with tumor metastasis and cancer-specific survival. Mol Med Camb Mass 2015; 21 (1): 381–388. doi: 10.2119/molmed.2014.00203.
Štítky
Paediatric clinical oncology Surgery Clinical oncologyČlánok vyšiel v časopise
Clinical Oncology
2016 Číslo 6
- Spasmolytic Effect of Metamizole
- Metamizole at a Glance and in Practice – Effective Non-Opioid Analgesic for All Ages
- Metamizole in perioperative treatment in children under 14 years – results of a questionnaire survey from practice
- Current Insights into the Antispasmodic and Analgesic Effects of Metamizole on the Gastrointestinal Tract
- Obstacle Called Vasospasm: Which Solution Is Most Effective in Microsurgery and How to Pharmacologically Assist It?
Najčítanejšie v tomto čísle
- Molecular Genetic Testing for Acute Myeloid Leukemia
- Molecular Pathogenesis of Colorectal Cancer
- Quality of Life, Anxiety and Depression in Patients with Differentiated Thyroid Cancer under Short Term Hypothyroidism Induced by Levothyroxine Withdrawal
- A Patient with Primary Intraventricular Gliosarcoma and Long-term Survival – a Case Report