Downregulation of miR‑505‑3p predicts poor bone metastasis‑free survival in prostate cancer

Tang,Yubo; Wu,Bowen; Huang,Shuai; Peng,Xinsheng; Li,Xing; Huang,Xiufang; Zhou,Wei; Xie,Peigen; He,Peiheng

doi:10.3892/or.2018.6826

Downregulation of miR‑505‑3p predicts poor bone metastasis‑free survival in prostate cancer

Authors:
- Yubo Tang
- Bowen Wu
- Shuai Huang
- Xinsheng Peng
- Xing Li
- Xiufang Huang
- Wei Zhou
- Peigen Xie
- Peiheng He
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Affiliations: Department of Pharmacy, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China, Department of Orthopedics, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510632, P.R. China, Department of Orthopaedic Surgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangzhou 510260, P.R. China , Department of Orthopaedic Surgery, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China , Department of Pathology, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat‑sen University, Jiangmen, Guangdong 529030, P.R. China , Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510000, P.R. China
Published online on: October 25, 2018 https://doi.org/10.3892/or.2018.6826
Pages: 57-66
Copyright: © Tang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The principal issue deriving from prostate cancer (PCa) is its propensity to metastasize to bone. To date, bone metastasis remains incurable, and therapeutic strategies are limited. Therefore, it is of paramount importance to explore predictive markers for bone metastasis of PCa. In the present study, we reported that miR‑505‑3p was significantly downregulated in bone metastatic PCa tissues compared with that in non‑bone metastatic PCa tissues, but there was no significant difference in miR‑505‑3p expression between PCa and adjacent normal tissues. miR‑505‑3p expression was inversely associated with serum PSA levels, Gleason grade, N and M classification, and short bone metastasis‑free survival in PCa patients, but had no effect on overall survival in PCa patients. Furthermore, upregulation of miR‑505‑3p suppressed the activity of TGF‑β signaling by directly targeting downstream effectors of TGF‑β signaling, SMAD2 and SMAD3, further inhibiting the invasion and migration abilities of PCa cells. Therefore, our findings unraveled a novel mechanism by which miR‑505‑3p inhibits bone metastasis of PCa, supporting the notion that miR‑505‑3p may serve as a predictive marker for bone metastasis of PCa.

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1	Nelson WG, De Marzo AM and Isaacs WB: Prostate cancer. N Engl J Med. 349:366–381. 2003. View Article : Google Scholar : PubMed/NCBI
2	Sabbatini P, Larson SM, Kremer A, Zhang ZF, Sun M, Yeung H, Imbriaco M, Horak I, Conolly M, Ding C, et al: Prognostic significance of extent of disease in bone in patients with androgen-independent prostate cancer. J Clin Oncol. 17:948–957. 1999. View Article : Google Scholar : PubMed/NCBI
3	Ventura A and Jacks T: MicroRNAs and cancer: Short RNAs go a long way. Cell. 136:586–591. 2009. View Article : Google Scholar : PubMed/NCBI
4	Khew-Goodall Y and Goodall GJ: Myc-modulated miR-9 makes more metastases. Nat cell Biol. 12:209–211. 2010. View Article : Google Scholar : PubMed/NCBI
5	Hao GJ, Ding YH, Wen H, Li XF, Zhang W, Su HY, Liu DM and Xie NL: Attenuation of deregulated miR-369-3p expression sensitizes non-small cell lung cancer cells to cisplatin via modulation of the nucleotide sugar transporter SLC35F5. Biochem Biophys Res Commun. 488:501–508. 2017. View Article : Google Scholar : PubMed/NCBI
6	Ren D, Lin B, Zhang X, Peng Y, Ye Z, Ma Y, Liang Y, Cao L, Li X, Li R, et al: Maintenance of cancer stemness by miR-196b-5p contributes to chemoresistance of colorectal cancer cells via activating STAT3 signaling pathway. Oncotarget. 8:49807–49823. 2017. View Article : Google Scholar : PubMed/NCBI
7	Zhao G, Li Y and Wang T: Potentiation of docetaxel sensitivity by miR-638 via regulation of STARD10 pathway in human breast cancer cells. Biochem Biophys Res Commun. 487:255–261. 2017. View Article : Google Scholar : PubMed/NCBI
8	Zhang X, Liu J, Zang D, Wu S, Liu A, Zhu J, Wu G, Li J and Jiang L: Upregulation of miR-572 transcriptionally suppresses SOCS1 and p21 and contributes to human ovarian cancer progression. Oncotarget. 6:15180–15193. 2015.PubMed/NCBI
9	Ren D, Yang Q, Dai Y, Guo W, Du H, Song L and Peng X: Oncogenic miR-210-3p promotes prostate cancer cell EMT and bone metastasis via NF-kappaB signaling pathway. Mol Cancer. 16:1172017. View Article : Google Scholar : PubMed/NCBI
10	Liu Z, Liu Z, Zhang Y, Li Y, Liu B and Zhang K: miR-24 represses metastasis of human osteosarcoma cells by targeting Ack1 via AKT/MMPs pathway. Biochem Biophys Res Commun. 486:211–217. 2017. View Article : Google Scholar : PubMed/NCBI
11	Siu MK, Tsai YC, Chang YS, Yin JJ, Suau F, Chen WY and Liu YN: Transforming growth factor-beta promotes prostate bone metastasis through induction of microRNA-96 and activation of the mTOR pathway. Oncogene. 34:4767–4776. 2015. View Article : Google Scholar : PubMed/NCBI
12	Ren D, Wang M, Guo W, Zhao X, Tu X, Huang S, Zou X and Peng X: Wild-type p53 suppresses the epithelial-mesenchymal transition and stemness in PC-3 prostate cancer cells by modulating miR145. Int J Oncol. 42:1473–1481. 2013. View Article : Google Scholar : PubMed/NCBI
13	Ren D, Wang M, Guo W, Huang S, Wang Z, Zhao X, Du H, Song L and Peng X: Double-negative feedback loop between ZEB2 and miR-145 regulates epithelial-mesenchymal transition and stem cell properties in prostate cancer cells. Cell Tissue Res. 358:763–778. 2014. View Article : Google Scholar : PubMed/NCBI
14	Guo W, Ren D, Chen X, Tu X, Huang S, Wang M, Song L, Zou X and Peng X: HEF1 promotes epithelial mesenchymal transition and bone invasion in prostate cancer under the regulation of microRNA-145. J Cell Biochem. 114:1606–1615. 2013. View Article : Google Scholar : PubMed/NCBI
15	Wang M, Ren D, Guo W, Huang S, Wang Z, Li Q, Du H, Song L and Peng X: N-cadherin promotes epithelial-mesenchymal transition and cancer stem cell-like traits via ErbB signaling in prostate cancer cells. Int J Oncol. 48:595–606. 2016. View Article : Google Scholar : PubMed/NCBI
16	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2^−ΔΔCT method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
17	Zhang X, Ren D, Guo L, Wang L, Wu S, Lin C, Ye L, Zhu J, Li J, Song L, et al: Thymosin beta 10 is a key regulator of tumorigenesis and metastasis and a novel serum marker in breast cancer. Breast cancer Res. 19:152017. View Article : Google Scholar : PubMed/NCBI
18	Zhang X, Zhang L, Lin B, Chai X, Li R, Liao Y, Deng X, Liu Q, Yang W, Cai Y, et al: Phospholipid phosphatase 4 promotes proliferation and tumorigenesis, and activates Ca²⁺-permeable cationic channel in lung carcinoma cells. Mol Cancer. 16:1472017. View Article : Google Scholar : PubMed/NCBI
19	Li X, Liu F, Lin B, Luo H, Liu M, Wu J, Li C, Li R, Zhang X, Zhou K, et al: miR150 inhibits proliferation and tumorigenicity via retarding G1/S phase transition in nasopharyngeal carcinoma. Int J Oncol. 2017.
20	Wang M, Ren D, Guo W, Wang Z, Huang S, Du H, Song L and Peng X: Loss of miR-100 enhances migration, invasion, epithelial-mesenchymal transition and stemness properties in prostate cancer cells through targeting Argonaute 2. Int J Oncol. 45:362–372. 2014. View Article : Google Scholar : PubMed/NCBI
21	Cheadle C, Vawter MP, Freed WJ and Becker KG: Analysis of microarray data using Z score transformation. J Mol Diagn. 5:73–81. 2003. View Article : Google Scholar : PubMed/NCBI
22	Agarwal V, Bell GW, Nam JW and Bartel DP: Predicting effective microRNA target sites in mammalian mRNAs. Elife. 4:2015. View Article : Google Scholar
23	Betel D, Wilson M, Gabow A, Marks DS and Sander C: The microRNA.org resource: Targets and expression. Nucleic Acids Res. 36:D149–D153. 2008. View Article : Google Scholar : PubMed/NCBI
24	Dai Y, Ren D, Yang Q, Cui Y, Guo W, Lai Y, Du H, Lin C, Li J, Song L, et al: The TGF-β signalling negative regulator PICK1 represses prostate cancer metastasis to bone. Br J Cancer. 117:685–694. 2017. View Article : Google Scholar : PubMed/NCBI
25	Xu M, Kuang Y, Wang M, Han X and Yang Q: A microRNA expression signature as a predictor of survival for colon adenocarcinoma. Neoplasma. 64:56–64. 2017. View Article : Google Scholar : PubMed/NCBI
26	Ma C, Xu B, Husaiyin S, Wang L, Wusainahong K, Ma J, Zhu K and Niyazi M: MicroRNA-505 predicts prognosis and acts as tumor inhibitor in cervical carcinoma with inverse association with FZD4. Biosmed Pharmacother. 92:586–594. 2017. View Article : Google Scholar
27	Lin XJ, Chong Y, Guo ZW, Xie C, Yang XJ, Zhang Q, Li SP, Xiong Y, Yuan Y, Min J, et al: A serum microRNA classifier for early detection of hepatocellular carcinoma: A multicentre, retrospective, longitudinal biomarker identification study with a nested case-control study. Lancet Oncol. 16:804–815. 2015. View Article : Google Scholar : PubMed/NCBI
28	Fournier PG, Juarez P, Jiang G, Clines GA, Niewolna M, Kim HS, Walton HW, Peng XH, Liu Y, Mohammad KS, et al: The TGF-beta signaling regulator PMEPA1 suppresses prostate cancer metastases to bone. Cancer Cell. 27:809–821. 2015. View Article : Google Scholar : PubMed/NCBI
29	No authors listed. TGF β induces a pro-bone metastasis program in prostate cancer. Cancer Discov. 5(OF23)2015.
30	Yin JJ, Selander K, Chirgwin JM, Dallas M, Grubbs BG, Wieser R, Massague J, Mundy GR and Guise TA: TGF-beta signaling blockade inhibits PTHrP secretion by breast cancer cells and bone metastases development. J Clin Invest. 103:197–206. 1999. View Article : Google Scholar : PubMed/NCBI
31	Kang Y, Siegel PM, Shu W, Drobnjak M, Kakonen SM, Cordon-Cardo C, Guise TA and Massague J: A multigenic program mediating breast cancer metastasis to bone. Cancer Cell. 3:537–549. 2003. View Article : Google Scholar : PubMed/NCBI
32	Sethi N, Dai X, Winter CG and Kang Y: Tumor-derived JAGGED1 promotes osteolytic bone metastasis of breast cancer by engaging Notch signaling in bone cells. Cancer Cell. 19:192–205. 2011. View Article : Google Scholar : PubMed/NCBI
33	Javelaud D, Mohammad KS, McKenna CR, Fournier P, Luciani F, Niewolna M, Andre J, Delmas V, Larue L, Guise TA, et al: Stable overexpression of Smad7 in human melanoma cells impairs bone metastasis. Cancer Res. 67:2317–2324. 2007. View Article : Google Scholar : PubMed/NCBI
34	Schaefer A, Jung M, Mollenkopf HJ, Wagner I, Stephan C, Jentzmik F, Miller K, Lein M, Kristiansen G and Jung K: Diagnostic and prognostic implications of microRNA profiling in prostate carcinoma. Int J Cancer. 126:1166–1176. 2010.PubMed/NCBI
35	Haflidadottir BS, Larne O, Martin M, Persson M, Edsjo 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
36	Chen S, Sun KX, Liu BL, Zong ZH and Zhao Y: MicroRNA-505 functions as a tumor suppressor in endometrial cancer by targeting TGF-alpha. Mol Cancer. 15:112016. View Article : Google Scholar : PubMed/NCBI
37	Skinner HD, Lee JH, Bhutani MS, Weston B, Hofstetter W, Komaki R, Shiozaki H, Wadhwa R, Sudo K, Elimova E, et al: A validated miRNA profile predicts response to therapy in esophageal adenocarcinoma. Cancer. 120:3635–3641. 2014. View Article : Google Scholar : PubMed/NCBI
38	Ramachandran SS, Muiwo P, Ahmad HM, Pandey RM, Singh S, Bakhshi S, Kumar L, Bhattacharya A and Gupta YK: miR-505-5p and miR-193b-3p: Potential biomarkers of imatinib response in patients with chronic myeloid leukemia. Leuk Lymphoma. 58:1981–1984. 2017. View Article : Google Scholar : PubMed/NCBI
39	Molina-Pinelo S, Carnero A, Rivera F, Estevez-Garcia P, Bozada JM, Limon ML, Benavent M, Gomez J, Pastor MD, Chaves M, et al: MiR-107 and miR-99a-3p predict chemotherapy response in patients with advanced colorectal cancer. BMC Cancer. 14:6562014. View Article : Google Scholar : PubMed/NCBI