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Loss of miR-516a-3p mediates upregulation of ABCC5 in prostate cancer and drives its progression

Authors Zhang H, Lian Z, Sun G, Liu R, Xu Y

Received 7 March 2018

Accepted for publication 4 June 2018

Published 6 July 2018 Volume 2018:11 Pages 3853—3867


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Jianmin Xu

Hongtuan Zhang, Zhenpeng Lian, Guangyu Sun, Ranlu Liu, Yong Xu

Department of Urology, National Key Specialty of Urology, The Second Hospital of Tianjin Medical University, Tianjin Key Institute of Urology, Tianjin Medical University, Tianjin, China

Abstract: To gain a comprehensive understanding of whether ABCC5 can regulate prostate cancer (PCa) progression, we performed microarray data analyses and identified that ABCC5 was drastically increased in primary PCa relative to normal samples, metastatic PCa relative to primary PCa, and castration-resistant PCa relative to hormone naïve PCa, respectively. Multivariate Cox regression analysis suggested that ABCC5 overexpression in PCa was an independent prognostic factor for both poor biochemical recurrence-free and overall survival. We demonstrated that ABCC5 knockdown significantly inhibits PCa cell proliferation, migration, and invasion in vitro and suppresses tumor growth and metastasis in vivo. We also demonstrated that miR-516a-3p was significantly downregulated in PCa. We finally demonstrated that ABCC5 was a direct target of miR-516a-3p. miR-516a-3p overexpression can phenotypically copy ABCC5 knockdown-induced phenotypes, whereas forced expression of ABCC5 can drastically reverse the inhibitory effects of miR-516a-3p. miR-516a-3p may modulate the sensitivity of cancer cells to adriamycin and docetaxel by targeting ABCC5 with important implications in the design of new therapeutic agents. Taken together, our results indicated that loss of miR-516a-3p expression and thus uncontrolled ABCC5 upregulation might drive PCa progression and influence chemosensitivity.

Keywords: ABCC5, miR-516a-3p, prostate cancer, metastasis, chemosensitivity

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