A feedback regulatory loop between HIF-1α and miR-21 in response to hypoxia in cardiomyocytes

Accumulating evidence suggests that hypoxia-inducible factor 1 alpha (HIF-1 alpha) regulates numerous miRNAs and is crucial for cellular response to hypoxia. However, the relationship between HIF-1 alpha and miR-21 in hypoxic cardiomyocytes is little known. We found that hypoxia induced HIF-1 alpha and miR-21 expression. HIF-1 alpha knockdown increased cell apoptosis and reduced miR-21 expression. Furthermore, we found that HIF-1 alpha transcriptionally enhanced miR-21 promoter activity by binding to its promoter, which required the recruitment of CBP/p300. In addition, we found that miR-21 inhibition increased cell apoptosis and reduced HIF-1 alpha expression, and modulated the PTEN/Akt pathway. Our results indicate that HIF-1 alpha-miR-21 feedback contributes to the adaptation of cardiomyocytes to hypoxia, and has potential as therapeutic target for myocardial ischemia. (C) 2014 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.