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

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.