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A feedback regulatory loop between HIF‐1α and miR‐21 in response to hypoxia in cardiomyocytes
Author(s) -
Liu Yang,
Nie Honggang,
Zhang Kuikui,
Ma Dan,
Yang Guang,
Zheng Zhilei,
Liu Kai,
Yu Bo,
Zhai Changlin,
Yang Shuang
Publication year - 2014
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2014.05.067
Subject(s) - hypoxia (environmental) , gene knockdown , apoptosis , microrna , microbiology and biotechnology , pten , hypoxia inducible factors , protein kinase b , cellular adaptation , cell , chemistry , biology , cancer research , pi3k/akt/mtor pathway , signal transduction , gene , biochemistry , organic chemistry , oxygen
Accumulating evidence suggests that hypoxia‐inducible factor 1α (HIF‐1α) regulates numerous miRNAs and is crucial for cellular response to hypoxia. However, the relationship between HIF‐1α and miR‐21 in hypoxic cardiomyocytes is little known. We found that hypoxia induced HIF‐1α and miR‐21 expression. HIF‐1α knockdown increased cell apoptosis and reduced miR‐21 expression. Furthermore, we found that HIF‐1α 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‐1α expression, and modulated the PTEN/Akt pathway. Our results indicate that HIF‐1α‐miR‐21 feedback contributes to the adaptation of cardiomyocytes to hypoxia, and has potential as therapeutic target for myocardial ischemia.