Downregulation of miR-199a-5p promotes prostate adeno-carcinoma progression through loss of its inhibition of HIF-1α

// Jinjing Zhong 1 , Rui Huang 2 , Zhengzheng Su 1 , Mengni Zhang 1 , Miao Xu 1 , Jing Gong 1 , Ni Chen 1 , Hao Zeng 3 , Xueqin Chen 1 and Qiao Zhou 1 1 Department of Pathology, West China Hospital and National Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041, China 2 Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu 610041, China 3 Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China Correspondence to: Xueqin Chen, email: cxq19761980@126.com Qiao Zhou, email: zhou_qiao@hotmail.com Keywords: prostate cancer, microRNA, miR-199a-5p, HIF-1α Received: February 08, 2017 Accepted: April 11, 2017 Published: May 31, 2017 ABSTRACT Hypoxia-inducible factor-1 alpha (HIF-1α) plays key roles in cell survival under both hypoxia and normoxia conditions. Regulation of HIF-1α is complex and involves numerous molecules and pathways, including post-transcriptional regulation by microRNAs (miRNAs). Although upregulation of HIF-1α has been shown to promote prostate adenocarcinoma (PCa) progression, the mechanism by which miRNAs modulate HIF-1α in prostate cancer has not been clarified. Here, we show that miR-199a-5p is underexpressed in prostate adenocarcinoma. Artificial overexpression of miR-199a-5p decreased cell proliferation, motility, and tumor angiogenesis and increased apoptosis in PCa cell liness PC-3 and DU145 by directly targeting the 3’-untranslated region (UTR) of HIF-1α mRNA, which reduced HIF-1α levels as well as downstream genes transactivated by HIF-1α (such as VEGF, CXCR4, BNIP3 and BCL-xL). Abnormalities of miR-199a-HIF regulation may contribute significantly to PCa pathogenesis and progression.