Journal
PLOS ONE
Volume 4, Issue 10, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0007629
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The regulation of HIF-1 alpha is considered to be realized by pVHL-mediated ubiquitin-26S proteasome pathway at a post-transcriptional level. The discovery of a class of small noncoding RNAs, called microRNAs, implies alternative mechanism of regulation of HIF-1 alpha. Here, we show that miR-20b plays an important role in fine-tuning the adaptation of tumor cells to oxygen concentration. The inhibition of miR-20b increased the protein levels of HIF-1 alpha and VEGF in normoxic tumor cells; the increase of miR-20b in hypoxic tumor cells, nevertheless, decreased the protein levels of HIF-1 alpha and VEGF. By using luciferase reporter vector system, we confirmed that miR-20b directly targeted the 3'UTR of Hif1a and Vegfa. On the other hand, the forced overexpression of HIF-1 alpha in normoxic tumor cells downregulated miR-20b expression. However, HIF-1 alpha knockdown in hypoxic tumor cells caused the increase of miR-20b. The differential expression of miR-20b has important biological significance in tumor cells, either enhancing the growth or favoring the survival of tumor cells upon the oxygen supply. Thus, we identify a novel molecular regulation mechanism through which miR-20b regulates HIF-1 alpha and VEGF and is regulated by HIF-1 alpha so to keep tumor cells adapting to different oxygen concentrations.
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