miR-129 predicts prognosis and inhibits cell growth in human prostate carcinoma

Xu,Song; Yi,Xiao‑Ming; Zhang,Zheng‑Yu; Ge,Jing‑Ping; Zhou,Wen‑Quan

doi:10.3892/mmr.2016.5859

miR-129 predicts prognosis and inhibits cell growth in human prostate carcinoma

Authors:
- Song Xu
- Xiao‑Ming Yi
- Zheng‑Yu Zhang
- Jing‑Ping Ge
- Wen‑Quan Zhou
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Affiliations: Department of Urology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu 210002, P.R. China
Published online on: October 19, 2016 https://doi.org/10.3892/mmr.2016.5859
Pages: 5025-5032
Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

MicroRNAs (miRNAs) are a class of small, well-conserved, non-coding RNAs that are increasingly identified as diagnostic and prognostic biomarkers in a number of cancers. Deregulated miR‑129 is closely associated with tumorigenesis and cancer progression. However, the potential role of miR‑129 in prostate cancer remains largely elusive. The present study investigated the role of miR‑129 as a prognostic biomarker for tumor progression and clinical prognosis in prostate cancer patients. The examined prostate cancer tissues exhibited a significant reduction in miR‑129 expression compared with the normal tissues (P=0.013). The expression levels of miR‑129 were negatively correlated with histological grade (P<0.001), high preoperative prostate‑specific antigen serum levels (P<0.001), pathological stage (P<0.001), high Gleason score (P<0.001), lymph node metastasis (P=0.002), angiolymphatic invasion (P=0.018), and biochemical recurrence (BCR; P=0.001). Use of the Kaplan‑Meier analysis demonstrated that low miR‑129 expression was closely associated with poorer BCR‑free survival. Multivariate survival analysis indicated that miR‑129 expression may be an independent prognostic marker for BCR‑free survival in prostate cancer patients (P<0.001). Overexpression of miR‑129 markedly attenuated prostate cancer cell growth by rescuing cell cycle‑regulated protein expression. The present study suggests that miR‑129 is downregulated in the cancerous tissues of prostate cancer patients, which was associated with poor BCR‑free survival. Thus, it may be considered as a novel independent prognostic biomarker for prostate cancer. In addition, downregulation of miR‑129 may serve a critical role in the proliferation of prostate cancer cells.

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1	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2013. CA Cancer J Clin. 63:11–30. 2013. View Article : Google Scholar : PubMed/NCBI
2	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
3	Ferlay J, Parkin DM and Steliarova-Foucher E: Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer. 46:765–781. 2010. View Article : Google Scholar : PubMed/NCBI
4	Carroll PR: Early stage prostate cancer-do we have a problem with over-detection, overtreatment or both? J Urol. 173:1061–1062. 2005. View Article : Google Scholar : PubMed/NCBI
5	Boehm K, Schiffmann J, Tian Z, Lesmana H, Larcher A, Mandel P, Karakiewicz PI, Graefen M, Schwarz R, Krüll A and Tilki D: Five-year biochemical recurrence-free and overall survival following high-dose-rate brachytherapy with additional external beam or radical prostatectomy in patients with clinically localized prostate cancer. Urol Oncol. 34:119.e11–e18. 2016. View Article : Google Scholar
6	Ishizaki F, Hara N, Koike H, Kawaguchi M, Tadokoro A, Takizawa I, Nishiyama T, Takahashi K and Hohenfellner R: Prediction of pathological and oncological outcomes based on extended prostate biopsy results in patients with prostate cancer receiving radical prostatectomy: A single institution study. Diagn Pathol. 7:682012. View Article : Google Scholar : PubMed/NCBI
7	Velonas VM, Woo HH, dos Remedios CG and Assinder SJ: Current status of biomarkers for prostate cancer. Int J Mol Sci. 14:11034–11060. 2013. View Article : Google Scholar : PubMed/NCBI
8	Moyer VA: U.S. Preventive Services Task Force: Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 157:120–134. 2012. View Article : Google Scholar : PubMed/NCBI
9	Dabir PD, Ottosen P, Hoyer S and Hamilton-Dutoit S: Comparative analysis of three- and two-antibody cocktails to AMACR and basal cell markers for the immunohistochemical diagnosis of prostate carcinoma. Diagn Pathol. 7:812012. View Article : Google Scholar : PubMed/NCBI
10	Humphrey PA and Vollmer RT: Percentage carcinoma as a measure of prostatic tumor size in radical prostatectomy tissues. Mod Pathol. 10:326–333. 1997.PubMed/NCBI
11	Friedman RC, Farh KK, Burge CB and Bartel DP: Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 19:92–105. 2009. View Article : Google Scholar : PubMed/NCBI
12	Li J, Ju J, Ni B and Wang H: The emerging role of miR-506 in cancer. Oncotarget. Aug 15–2016.(Epub ahead of print).
13	Pallante P, Visone R, Ferracin M, Ferraro A, Berlingieri MT, Troncone G, Chiappetta G, Liu CG, Santoro M, Negrini M, et al: MicroRNA deregulation in human thyroid papillary carcinomas. Endocr Relat Cancer. 13:497–508. 2006. View Article : Google Scholar : PubMed/NCBI
14	Ohtsuka M, Ling H, Doki Y, Mori M and Calin GA: MicroRNA processing and human cancer. J Clin Med. 4:1651–1667. 2015. View Article : Google Scholar : PubMed/NCBI
15	Zhai J, Qu S, Li X, Zhong J, Chen X, Qu Z and Wu D: miR-129 suppresses tumor cell growth and invasion by targeting PAK5 in hepatocellular carcinoma. Biochem Biophys Res Commun. 464:161–167. 2015. View Article : Google Scholar : PubMed/NCBI
16	Xiao Y, Li X, Wang H, Wen R, He J and Tang J: Epigenetic regulation of miR-129-2 and its effects on the proliferation and invasion in lung cancer cells. J Cell Mol Med. 19:2172–2180. 2015.PubMed/NCBI
17	Malik AY and Foster C: The revised declaration of Helsinki: Cosmetic or real change? J R Soc Med. 109:184–189. 2016. View Article : Google Scholar : PubMed/NCBI
18	Miah S, Ahmed HU, Freeman A and Emberton M: Does true Gleason pattern 3 merit its cancer descriptor? Nat Rev Urol. 13:541–548. 2016. View Article : Google Scholar : PubMed/NCBI
19	Xu S, Yi XM, Zhou WQ, Cheng W, Ge JP and Zhang ZY: Downregulation of miR-129 in peripheral blood mononuclear cells is a diagnostic and prognostic biomarker in prostate cancer. Int J Clin Exp Pathol. 8:14335–14344. 2015.PubMed/NCBI
20	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
21	Wang QY, Tang J, Zhou CX and Zhao Q: The down-regulation of miR-129 in breast cancer and its effect on breast cancer migration and motility. Sheng Li Xue Bao. 64:403–411. 2012.(In Chinese). PubMed/NCBI
22	Wilson HC, Shah SI, Abel PD, Price P, Honeyfield L, Edwards S and Abel RL: Contemporary hormone therapy with LHRH agonists for prostate cancer: Avoiding osteoporosis and fracture. Cent European J Urol. 68:165–168. 2015.PubMed/NCBI
23	Mapelli P and Picchio M: Initial prostate cancer diagnosis and disease staging-the role of choline-PET-CT. Nat Rev Urol. 12:510–518. 2015. View Article : Google Scholar : PubMed/NCBI
24	Molitierno J, Evans A, Mohler JL, Wallen E, Moore D and Pruthi RS: Characterization of biochemical recurrence after radical prostatectomy. Urol Int. 77:130–134. 2006. View Article : Google Scholar : PubMed/NCBI
25	Montironi R, Mazzuccheli R, Scarpelli M, Lopez-Beltran A, Fellegara G and Algaba F: Gleason grading of prostate cancer in needle biopsies or radical prostatectomy specimens: Contemporary approach, current clinical significance and sources of pathology discrepancies. BJU Int. 95:1146–1152. 2005. View Article : Google Scholar : PubMed/NCBI
26	Hua X, Yu L, Pan W, Huang X, Liao Z, Xian Q, Fang L and Shen H: Increased expression of Golgi phosphoprotein-3 is associated with tumor aggressiveness and poor prognosis of prostate cancer. Diagn Pathol. 7:1272012. View Article : Google Scholar : PubMed/NCBI
27	Jonsson L, Gaber A, Ulmert D, Uhlén M, Bjartell A and Jirström K: High RBM3 expression in prostate cancer independently predicts a reduced risk of biochemical recurrence and disease progression. Diagn Pathol. 6:912011. View Article : Google Scholar : PubMed/NCBI
28	Diao Y, Wu D, Dai Z, Kang H, Wang Z and Wang X: Prognostic value of transformer 2β expression in prostate cancer. Int J Clin Exp Pathol. 8:6967–6973. 2015.PubMed/NCBI
29	Sempere LF: Integrating contextual miRNA and protein signatures for diagnostic and treatment decisions in cancer. Expert Rev Mol Diagn. 11:813–827. 2011. View Article : Google Scholar : PubMed/NCBI
30	Zhang H, Qi S, Zhang T, Wang A, Liu R, Guo J, Wang Y and Xu Y: miR-188-5p inhibits tumour growth and metastasis in prostate cancer by repressing LAPTM4B expression. Oncotarget. 6:6092–6104. 2015. View Article : Google Scholar : PubMed/NCBI
31	Spahn M, Kneitz S, Scholz CJ, Stenger N, Rüdiger T, Ströbel P, Riedmiller H and Kneitz B: Expression of microRNA-221 is progressively reduced in aggressive prostate cancer and metastasis and predicts clinical recurrence. Int J Cancer. 127:394–403. 2010.PubMed/NCBI
32	Haflidadóttir BS, Larne O, Martin M, Persson M, Edsjö A, Bjartell A and Ceder Y: Upregulation of miR-96 enhances cellular proliferation of prostate cancer cells through FOXO1. PloS One. 8:e724002013. View Article : Google Scholar : PubMed/NCBI
33	Fesler A, Zhai H and Ju J: miR-129 as a novel therapeutic target and biomarker in gastrointestinal cancer. Onco Targets Ther. 7:1481–1485. 2014.PubMed/NCBI
34	Tsai KW, Wu CW, Hu LY, Li SC, Liao YL, Lai CH, Kao HW, Fang WL, Huang KH, Chan WC and Lin WC: Epigenetic regulation of miR-34b and miR-129 expression in gastric cancer. Int J Cancer. 129:2600–2610. 2011. View Article : Google Scholar : PubMed/NCBI
35	Bandres E, Agirre X, Bitarte N, Ramirez N, Zarate R, Roman-Gomez J, Prosper F and Garcia-Foncillas J: Epigenetic regulation of microRNA expression in colorectal cancer. Int J Cancer. 125:2737–2743. 2009. View Article : Google Scholar : PubMed/NCBI
36	Chen X, Zhang L, Zhang T, Hao M, Zhang X, Zhang J, Xie Q, Wang Y, Guo M, Zhuang H and Lu F: Methylation-mediated repression of microRNA 129-2 enhances oncogenic SOX4 expression in HCC. Liver Int. 33:476–486. 2013. View Article : Google Scholar : PubMed/NCBI
37	Chen X, Ruan A, Wang X, Han W, Wang R, Lou N, Ruan H, Qiu B, Yang H and Zhang X: miR-129-3p, as a diagnostic and prognostic biomarker for renal cell carcinoma, attenuates cell migration and invasion via downregulating multiple metastasis-related genes. J Cancer Res Clin Oncol. 140:1295–1304. 2014. View Article : Google Scholar : PubMed/NCBI
38	Dyrskjot L, Ostenfeld MS, Bramsen JB, Silahtaroglu AN, Lamy P, Ramanathan R, Fristrup N, Jensen JL, Andersen CL, Zieger K, et al: Genomic profiling of microRNAs in bladder cancer: miR-129 is associated with poor outcome and promotes cell death in vitro. Cancer Res. 69:4851–4860. 2009. View Article : Google Scholar : PubMed/NCBI
39	Goździk-Spychalska J, Szyszka-Barth K, Spychalski L, Ramlau K, Wójtowicz J, Batura-Gabryel H and Ramlau R: C-MET inhibitors in the treatment of lung cancer. Curr Treat Options Oncol. 15:670–682. 2014. View Article : Google Scholar : PubMed/NCBI
40	Duan L, Hao X, Liu Z, Zhang Y and Zhang G: MiR-129-5p is down-regulated and involved in the growth, apoptosis and migration of medullary thyroid carcinoma cells through targeting RET. FEBS Lett. 588:1644–1651. 2014. View Article : Google Scholar : PubMed/NCBI
41	Yang Y, Pan X, Lei W, Wang J, Shi J, Li F and Song J: Regulation of transforming growth factor-beta 1-induced apoptosis and epithelial-to-mesenchymal transition by protein kinase A and signal transducers and activators of transcription 3. Cancer Res. 66:8617–8624. 2006. View Article : Google Scholar : PubMed/NCBI
42	Bao B, Ahmad A, Kong D, Ali S, Azmi AS, Li Y, Banerjee S, Padhye S and Sarkar FH: Hypoxia induced aggressiveness of prostate cancer cells is linked with deregulated expression of VEGF, IL-6 and miRNAs that are attenuated by CDF. PloS One. 7:e437262012. View Article : Google Scholar : PubMed/NCBI
43	Abukhdeir AM and Park BH: P21 and p27: Roles in carcinogenesis and drug resistance. Expert Rev Mol Med. 10:e192008. View Article : Google Scholar : PubMed/NCBI
44	Fu M, Wang C, Li Z, Sakamaki T and Pestell RG: Minireview: Cyclin D1: Normal and abnormal functions. Endocrinology. 145:5439–5447. 2004. View Article : Google Scholar : PubMed/NCBI
45	Hashimoto Y, Naruyama H, Ando R, Okada S, Tozawa K and Kohri K: Molecular targeted therapy for prostate cancer. Hinyokika Kiyo. 54:57–61. 2008.PubMed/NCBI
46	Lee JT, Lehmann BD, Terrian DM, Chappell WH, Stivala F, Libra M, Martelli AM, Steelman LS and McCubrey JA: Targeting prostate cancer based on signal transduction and cell cycle pathways. Cell Cycle. 7:1745–1762. 2008. View Article : Google Scholar : PubMed/NCBI