Research Papers:
Downregulation of miR199a5p promotes prostate adenocarcinoma progression through loss of its inhibition of HIF1α
PDF | Full Text | How to cite
Metrics: PDF 2547 views | Full Text 4932 views
Jinjing Zhong1, Rui Huang2, Zhengzheng Su1, Mengni Zhang1, Miao Xu1, Jing Gong1, Ni Chen1, Hao Zeng3, Xueqin Chen1 and Qiao Zhou1
1Department of Pathology, West China Hospital and National Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041, China
2Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu 610041, China
3Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
Correspondence to:
Xueqin Chen, email: [email protected]
Qiao Zhou, email: [email protected]
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.