Open AccessRegulation of HIF-1α and VEGF by miR-20b Tunes Tumor Cells to Adapt to the Alteration of Oxygen Concentration
Author(s) -
Lei Zhang,
Bo Li,
Zhonghan Yang,
Haoshu Fang,
Guimei Zhang,
Zuo-Hua Feng,
Bo Huang
Publication year - 2009
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0007629
Subject(s) - oxygen , vegf receptors , reactive oxygen species , oxygen metabolism , microbiology and biotechnology , chemistry , cancer research , biology , organic chemistry
The regulation of HIF-1α 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-1α. 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-1α and VEGF in normoxic tumor cells; the increase of miR-20b in hypoxic tumor cells, nevertheless, decreased the protein levels of HIF-1α 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-1α in normoxic tumor cells downregulated miR-20b expression. However, HIF-1α 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-1α and VEGF and is regulated by HIF-1α so to keep tumor cells adapting to different oxygen concentrations.