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Down-regulation of Dicer and Ago2 is associated with cell proliferation and apoptosis in prostate cancer

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Tumor Biology

Abstract

Dicer and Argonaute2 (Ago2) are critical components responsible not only for RNA interference but also for microRNA synthesis. The present study investigated the roles of Dicer and Ago2 in prostate cancer (Pca). First, the expression levels of Dicer and Ago2 in Pca tissues were determined by immunohistochemistry (IHC) and compared with pathological features. Next, RNA interference was used to down-regulate the expression levels of Dicer and Ago2 in the Pca cell lines LNCaP, PC-3, and DU145, and effects on proliferation, apoptosis, and cell cycle were detected using the CCK-8 assay and flow cytometry, respectively. We found that Dicer and Ago2 expression levels in Pca tissues were higher than those in adjacent benign tissues and correlated with lower Gleason patterns, with the exception of Dicer expression in localized Pca. In vitro, silencing Dicer or Ago2 inhibited cell proliferation and induced apoptosis in LNCaP, PC-3, and DU145, as well as arrested the cell cycle at the G2/M phase in androgen-dependent LNCaP, or at S phase in the androgen-independent PC-3 and DU145. Altogether these findings suggest that Dicer and Ago2 play important roles in proliferation, apoptosis, and the cell cycle in Pca and might serve as both promising biomarkers for Pca progression and potential therapeutic targets.

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References

  1. Center MM, Jemal A, Lortet-Tieulent J, Ward E, Ferlay J, Brawley O, et al. International variation in prostate cancer incidence and mortality rates. Eur Urol. 2012;61:1079–92.

    Article  PubMed  Google Scholar 

  2. Sakurai K, Amarzguioui M, Kim D-H, Alluin J, Heale B, Song M-s, et al. A role for human dicer in pre-RISC loading of siRNAs. Nucleic acids research. 2011;39:1510–25.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Kala R, Peek G, Hardy T, Tollefsbol T. MicroRNAs: an emerging science in cancer epigenetics. Journal of Clinical Bioinformatics. 2013;3:6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Peters L, Meister G. Argonaute proteins: mediators of RNA silencing. Molecular Cell. 2007;26:611–23.

    Article  CAS  PubMed  Google Scholar 

  5. Kim VN, Han J, Siomi MC. Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol. 2009;10:126–39.

    Article  CAS  PubMed  Google Scholar 

  6. Papachristou D, Korpetinou A, Giannopoulou E, Antonacopoulou A, Papadaki H, Grivas P, et al. Expression of the ribonucleases Drosha, Dicer, and Ago2 in colorectal carcinomas. Virchows Archiv : an international journal of pathology. 2011;459:431–40.

    Article  CAS  Google Scholar 

  7. Papachristou D, Sklirou E, Corradi D, Grassani C, Kontogeorgakos V, Rao U. Immunohistochemical analysis of the endoribonucleases Drosha, Dicer and Ago2 in smooth muscle tumours of soft tissues. Histopathology. 2012;60:36.

    Article  Google Scholar 

  8. Faggad A, Kasajima A, Weichert W, Stenzinger A, Elwali N. Dietel M, et al. Histopathology: Down-regulation of the microRNA processing enzyme Dicer is a prognostic factor in human colorectal cancer; 2012.

    Google Scholar 

  9. Khoshnaw S, Rakha E, Abdel-Fatah T, Nolan C, Hodi Z, Macmillan D, et al. Loss of Dicer expression is associated with breast cancer progression and recurrence. Breast Cancer Research and Treatment. 2012;135:403–13.

    Article  CAS  PubMed  Google Scholar 

  10. Zhang B, Chen H, Zhang L, Dakhova O, Zhang Y, Lewis MT, et al. A dosage-dependent pleiotropic role of Dicer in prostate cancer growth and metastasis. Oncogene. 2014;33:3099–108.

    Article  CAS  PubMed  Google Scholar 

  11. Zhang X, Graves P, Zeng Y. Overexpression of human argonaute2 inhibits cell and tumor growth. Biochimica et Biophysica Acta. 1830;2012:2553–61.

    Google Scholar 

  12. Shi TY, Yang G, Tu XY, Yang JM, Qian J, Wu XH, et al. Rad52 variants predict platinum resistance and prognosis of cervical cancer. PLoS One. 2012;7:e50461.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Chiosea S, Jelezcova E, Chandran U, Acquafondata M, McHale T, Sobol R, et al. Up-regulation of Dicer, a component of the microRNA machinery, in prostate adenocarcinoma. The American Journal of Pathology. 2006;169:1812–20.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Yoo N, Hur S, Kim M, Lee J, Lee S. Immunohistochemical analysis of RNA-induced silencing complex-related proteins ago2 and tnrc6a in prostate and esophageal cancers. APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica. 2010;118:271–6.

    Article  PubMed  Google Scholar 

  15. Boyd L, Mao X, Lu Y-J. The complexity of prostate cancer: genomic alterations and heterogeneity. Nature Reviews Urology. 2012;9:652–64.

    Article  PubMed  Google Scholar 

  16. Gregory RI, Shiekhattar R. MicroRNA biogenesis and cancer. Cancer Res. 2005;65:3509–12.

    Article  CAS  PubMed  Google Scholar 

  17. Croce CM, Calin GA. MiRNAs, cancer, and stem cell division. Cell. 2005;122:6–7.

    Article  CAS  PubMed  Google Scholar 

  18. Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A. 2006;103:2257–61.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Oh YK, Park TG. SiRNA delivery systems for cancer treatment. Adv Drug Deliv Rev. 2009;61:850–62.

    Article  CAS  PubMed  Google Scholar 

  20. Han L, Zhang A, Zhou X, Xu P, Wang G-X, Pu P-Y, et al. Downregulation of Dicer enhances tumor cell proliferation and invasion. International Journal of Oncology. 2010;37:299–305.

    CAS  PubMed  Google Scholar 

  21. Bai Y, Qiu G-R, Zhou F, Gong L-Y, Gao F, Sun K-L. Overexpression of Dicer1 induced by the upregulation of gata1 contributes to the proliferation and apoptosis of leukemia cells. International Journal of Oncology. 2013;42:1317–24.

    CAS  PubMed  Google Scholar 

  22. Naoghare P, Tak Y, Kim M, Han E, Song J. Knock-down of argonaute 2 (ago2) induces apoptosis in myeloid leukaemia cells and inhibits siRNA-mediated silencing of transfected oncogenes in hek-293 cells. Basic & Clinical Pharmacology & Toxicology. 2011;109:274–82.

    Article  CAS  Google Scholar 

  23. Asai T, Suzuki Y, Matsushita S, Yonezawa S, Yokota J, Katanasaka Y, et al. Disappearance of the angiogenic potential of endothelial cells caused by argonaute2 knockdown. Biochemical and Biophysical Research Communications. 2008;368:243–8.

    Article  CAS  PubMed  Google Scholar 

  24. McLoughlin H, Fineberg S, Ghosh L, Tecedor L, Davidson B. Dicer is required for proliferation, viability, migration and differentiation in corticoneurogenesis. Neuroscience. 2012;223:285–95.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Narayanan R, Jiang J, Gusev Y, Jones A, Kearbey J, Miller D, et al. MicroRNAs are mediators of androgen action in prostate and muscle. PloS One. 2010. doi:10.1371/journal.pone.0013637.

    Google Scholar 

  26. Carthew R, Sontheimer E. Origins and mechanisms of miRNAs and siRNAs. Cell. 2009;136:642–55.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Koscianska E, Starega-Roslan J, Krzyzosiak W. The role of Dicer protein partners in the processing of microRNA precursors. PloS one 2011;6

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Acknowledgments

This study was supported in part by grants from the National Natural Science Foundation of China (No. 81272837) and the Advanced Technology Foundation of Shanghai Hospitals (SHDC12013122).

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Correspondence to Ding-Wei Ye.

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**ao-Jie Bian and Gui-Ming Zhang contributed equally to this work.

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Bian, XJ., Zhang, GM., Gu, CY. et al. Down-regulation of Dicer and Ago2 is associated with cell proliferation and apoptosis in prostate cancer. Tumor Biol. 35, 11571–11578 (2014). https://doi.org/10.1007/s13277-014-2462-3

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  • DOI: https://doi.org/10.1007/s13277-014-2462-3

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