miR-34a inhibits cell proliferation in prostate cancer by downregulation of SIRT1 expression

Duan,Kun; Ge,Yong‑Chao; Zhang,Xue‑Pei; Wu,Shu‑Yi; Feng,Jin‑Shun; Chen,Shi‑Lin; Zhang,Li; Yuan,Zhi‑Hao; Fu,Chao‑Hong

doi:10.3892/ol.2015.3645

miR-34a inhibits cell proliferation in prostate cancer by downregulation of SIRT1 expression

Authors:
- Kun Duan
- Yong‑Chao Ge
- Xue‑Pei Zhang
- Shu‑Yi Wu
- Jin‑Shun Feng
- Shi‑Lin Chen
- Li Zhang
- Zhi‑Hao Yuan
- Chao‑Hong Fu
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Affiliations: Department of Urology Surgery, The Third People's Hospital of Zhengzhou, Zhengzhou, Henan, P.R. China, Department of Urology Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China, Department of Stem Cell and Organ Transplantation Laboratory, The Third People's Hospital of Zhengzhou, Zhengzhou, Henan, P.R. China
Published online on: August 26, 2015 https://doi.org/10.3892/ol.2015.3645
Pages: 3223-3227

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Abstract

MicroRNA-34a (miR-34a) functions as a tumor suppressor gene and inhibits abnormal cell growth by regulating the expression of other genes. The role of miR‑34a in regulating sirtuin 1 (SIRT1) in prostate cancer remains unclear. The objective of the present study was to investigate the biological function and molecular mechanisms of miR‑34a regulation of SIRT1 in human prostate cancer samples and the human prostate cancer cell line, PC‑3. Fresh prostate tissues were obtained from patients, and the miR‑34a expression in prostate cancer tissues was measured using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). qPCR and western blotting were performed to assess the effects of miR‑34a overexpression on SIRT1 regulation in PC‑3 cells, and the cell growth was assessed by Cell Counting Kit‑8 (CCK‑8). Flow cytometry was used to assess the cell cycle status of the cells. The miR‑34a expression levels in prostate cancer tissues were significantly reduced compared with adjacent normal prostate tissues (P<0.05). SIRT1 expression levels in PC‑3 cells with over‑expression of miR‑34a were significantly reduced compared with those in the negative control (P<0.05). The over‑expression of miR‑34a inhibited PC‑3 cells growth and resulted in increased cell cycle arrest compared with the negative control (P<0.05). In conclusion, miR‑34a inhibits the human prostate cancer cell proliferation, in part, through the downregulation of SIRT1 expression.

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1	Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D and Bray F: Cancer incidence and mortality worldwide: Sources, methods, and major patterns in GLOBOCAN 2012. Int J Cancer. 136:E359–E386. 2015. View Article : Google Scholar : PubMed/NCBI
2	Gade TP, Hassen W, Santos E, Gunset G, Saudemont A, Gong MC, Brentjens R, Zhong XS, Stephan M, Stefanski J, et al: Targeted elimination of prostate cancer by genetically directed human T lymphocytes. Cancer Res. 65:9080–9088. 2005. View Article : Google Scholar : PubMed/NCBI
3	Salter KH, Acharya CR, Walters KS, Redman R, Anguiano A, Garman KS, Anders CK, Mukherjee S, Dressman HK, Barry WT, et al: An integrated approach to the prediction of chemotherapeutic response in patients with breast cancer. PLoS One. 3:e19082008. View Article : Google Scholar : PubMed/NCBI
4	Denli AM, Tops BB, Plasterk RH, Ketting RF and Hannon GJ: Processing of primary microRNAs by the Microprocessor complex. Nature. 432:231–235. 2004. View Article : Google Scholar : PubMed/NCBI
5	Huntzinger E and Izaurralde E: Gene silencing by microRNAs: Contributions of translational repression and mRNA decay. Nat Rev Genet. 12:99–110. 2011. View Article : Google Scholar : PubMed/NCBI
6	Kloosterman WP and Plasterk RH: The diverse functions of microRNAs in animal development and disease. Dev Cell. 11:441–450. 2006. View Article : Google Scholar : PubMed/NCBI
7	Li XJ, Ren ZJ and Tang JH: MicroRNA-34a: A potential therapeutic target in human cancer. Cell Death Dis. 5:e13272014. View Article : Google Scholar : PubMed/NCBI
8	Guessous F, Zhang Y, Kofman A, Catania A, Li Y, Schiff D, Purow B and Abounader R: MicroRNA-34a is tumor suppressive in brain tumors and glioma stem cells. Cell Cycle. 9:1031–1036. 2010. View Article : Google Scholar : PubMed/NCBI
9	Ji Q, Hao X, Meng Y, Zhang M, Desano J, Fan D and Xu L: Restoration of tumor suppressor miR-34 inhibits human p53-mutant gastric cancer tumorspheres. BMC Cancer. 8:2662008. View Article : Google Scholar : PubMed/NCBI
10	Maroof H, Salajegheh A, Smith RA and Lam AK: Role of microRNA-34 family in cancer with particular reference to cancer angiogenesis. Exp Mol Pathol. 97:298–304. 2014. View Article : Google Scholar : PubMed/NCBI
11	Satoh A, Stein L and Imai S: The role of mammalian sirtuins in the regulation of metabolism, aging and longevity. Handb Exp Pharmacol. 206:125–162. 2011. View Article : Google Scholar : PubMed/NCBI
12	Kabra N, Li Z, Chen L, Li B, Zhang X, Wang C, Yeatman T, Coppola D and Chen J: SirT1 is an inhibitor of proliferation and tumor formation in colon cancer. J Biol Chem. 284:18210–18217. 2009. View Article : Google Scholar : PubMed/NCBI
13	Jung W, Hong KD, Jung WY, Lee E, Shin BK, Kim HK, Kim A and Kim BH: SIRT1 Expression Is Associated with Good Prognosis in Colorectal Cancer. Korean J Pathol. 47:332–339. 2013. View Article : Google Scholar : PubMed/NCBI
14	Kim JR, Moon YJ, Kwon KS, Bae JS, Wagle S, Yu TK, Kim KM, Park HS, Lee JH, Moon WS, et al: Expression of SIRT1 and DBC1 is associated with poor prognosis of soft tissue sarcomas. PLoS One. 8:e747382013. View Article : Google Scholar : PubMed/NCBI
15	Leko V, Park G, Lao U, et al: Enterocyte-specific inactivation of SIRT1 reduces tumor load in the APC (+/min) mouse model. PLoS One. 8:e662832013. View Article : Google Scholar : PubMed/NCBI
16	Knight JR, Allison SJ and Milner J: Active regulator of SIRT1 is required for cancer cell survival but not for SIRT1 activity. Open Biol. 3:130–135. 2013. View Article : Google Scholar
17	Revollo JR and Li X: The ways and means that fine tune SIRT1 activity. Trends Biochem Sci. 38:160–167. 2013. View Article : Google Scholar : PubMed/NCBI
18	Zhang XL, Chen ML and Zhou SL: Fentanyl increases colorectal carcinoma cell apoptosis by inhibition of NF-κB in a Sirt1-dependent manner. Asian Pac J Cancer Prev. 15:10015–10020. 2014. View Article : Google Scholar : PubMed/NCBI
19	The American Joint Committee on Cancer: The 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 17:1471–1474. 2010. View Article : Google Scholar : PubMed/NCBI
20	Welch C, Chen Y and Stallings RL: MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells. Oncogene. 26:5017–5022. 2007. View Article : Google Scholar : PubMed/NCBI
21	Moretti RM, Mareli M Montagnani, Taylor DM, Martini PG, Marzagalli M and Limonta P: Gonadotropin-releasing hormone agonists sensitize and resensitize, prostate cancer cells to docetaxel in a p53-dependent manner. PLoS One. 9:e937132014. View Article : Google Scholar : PubMed/NCBI
22	Lodygin D, Tarasov V, Epanchintsev A, Berking C, Knyazeva T, Körner H, Knyazev P, Diebold J and Hermeking H: Inactivation of miR-34a by aberrant CpG methylation in multiple types of cancer. Cell Cycle. 7:2591–2600. 2008. View Article : Google Scholar : PubMed/NCBI
23	Yamakuchi M, Ferlito M and Lowenstein CJ: MiR-34a repression of SIRT1 regulates apoptosis. Proc Natl Acad Sci U S A. 105:13421–13426. 2008. View Article : Google Scholar : PubMed/NCBI
24	Hwang BJ, Madabushi A, Jin J, Lin SY and Lu AL: Histone/protein deacetylase SIRT1 is an anticancer therapeutic target. Am J Cancer Res. 4:211–221. 2014.PubMed/NCBI
25	Zhao T, Li J and Chen AF: MicroRNA-34a induces endothelial progenitor cell senescence and impedes its angiogenesis via suppressing silent information regulator 1. Am J Physiol Endocrinol Metab. 299:E110–E116. 2010. View Article : Google Scholar : PubMed/NCBI
26	Akao Y, Noguchi S, Iio A, Kojima K, Takagi T and Naoe T: Dysregulation of microRNA-34a expression causes drug-resistance to 5-FU in human colon cancer DLD-1 cells. Cancer Lett. 300:197–204. 2011. View Article : Google Scholar : PubMed/NCBI
27	Li L, Yuan L, Luo J, Gao J, Guo J and Xie X: MiR-34a inhibits proliferation and migration of breast cancer through down-regulation of Bcl-2 and SIRT1. Clin Exp Med. 13:109–117. 2013. View Article : Google Scholar : PubMed/NCBI
28	Chapman EJ, Kelly G and Knowles MA: Genes involved in differentiation, stem cell renewal and tumorigenesis are modulated in telomerase-immortalized human urothelial cells. Mol Cancer Res. 6:1154–1168. 2008. View Article : Google Scholar : PubMed/NCBI
29	Audrito V, Rossi D, Gottardi D, et al: Nicotinamide blocks proliferation and induces apoptosis of chronic lymphocytic leukemia cells through activation of the p53/miR-34a/SIRT1 tumor suppressor network. Cancer Res. 71:4473–4483. 2011. View Article : Google Scholar : PubMed/NCBI
30	Bommer GT, Feng Y, Kaczorowski AJ, Gerin I, Kuick R, Love RE, Zhai Y, Giordano TJ, et al: p53-mediated activation of miRNA34 candidate tumor-suppressor genes. Curr Biol. 17:1298–1307. 2007. View Article : Google Scholar : PubMed/NCBI
31	Chen F and Hu SJ: Effect of microRNA-34a in cell cycle, differentiation and apoptosis: A review. J Biochem Mol Toxicol. 26:79–86. 2012. View Article : Google Scholar : PubMed/NCBI
32	Ito T, Yagi S and Yamakuchi M: MicroRNA-34a regulation of endothelial senescence. Biochem Biophys Res Commun. 398:735–740. 2010. View Article : Google Scholar : PubMed/NCBI