期刊
ONCOTARGET
卷 8, 期 48, 页码 83523-83538出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.18315
关键词
prostate cancer; microRNA; miR-199a-5p; HIF-1 alpha
资金
- National Science Foundation of China [NSFC 81572540, 81572541, 81272820, 81272848, 81302225, 81402110]
Hypoxia-inducible factor-1 alpha (HIF-1 alpha) plays key roles in cell survival under both hypoxia and normoxia conditions. Regulation of HIF-1 alpha is complex and involves numerous molecules and pathways, including post-transcriptional regulation by microRNAs (miRNAs). Although upregulation of HIF-1 alpha has been shown to promote prostate adenocarcinoma (PCa) progression, the mechanism by which miRNAs modulate HIF-1 alpha 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-1 alpha mRNA, which reduced HIF-1 alpha levels as well as downstream genes transactivated by HIF-1 alpha (such as VEGF, CXCR4, BNIP3 and BCL-xL). Abnormalities of miR-199a-HIF regulation may contribute significantly to PCa pathogenesis and progression.
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