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Regulation of HIF-1alpha and VEGF by miR-20b tunes tumor cells to adapt to the alteration of oxygen concentration

Regulation of HIF-1alpha and VEGF by miR-20b tunes tumor cells to adapt to the alteration of oxygen concentration

Authors :
Zhang Lei
Haoshu Fang
Zhuoshun Yang
Zuo-Hua Feng
Bo Li
Bo Huang
Gui-Mei Zhang
Source :
PLoS ONE, PLoS ONE, Vol 4, Iss 10, p e7629 (2009)
Publication Year :
2009

Abstract

The regulation of HIF-1alpha 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-1alpha. 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-1alpha and VEGF in normoxic tumor cells; the increase of miR-20b in hypoxic tumor cells, nevertheless, decreased the protein levels of HIF-1alpha 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-1alpha in normoxic tumor cells downregulated miR-20b expression. However, HIF-1alpha 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-1alpha and VEGF and is regulated by HIF-1alpha so to keep tumor cells adapting to different oxygen concentrations.

Details

ISSN :
19326203
Volume :
4
Issue :
10
Database :
OpenAIRE
Journal :
PloS one
Accession number :
edsair.doi.dedup.....db807a12595c0e4f7bcd501987f942bf