title: A feedback regulatory loop between HIF-1α and miR-21 in response to hypoxia in cardiomyocytes.
abstract: 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.
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China; Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, Harbin 150086, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China; Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, Harbin 150086, China.
authors.forename: Honggang
authors.initials: H
authors.lastname: Nie
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin 150086, China.
authors.forename: Kuikui
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China; Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, Harbin 150086, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Ma
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
authors.forename: Zhilei
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China; Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, Harbin 150086, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China; Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, Harbin 150086, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yu
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Jiaxing University, Jiaxing 314000, China. Electronic address: yesterdaygun@126.com.
authors.forename: Changlin
authors.initials: C
authors.lastname: Zhai
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China; Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, Harbin 150086, China. Electronic address: yangshuang0101_a@163.com.
authors.forename: Shuang
authors.initials: S
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects; D002460:Cell Line; D003035:Cobalt / Q000494:pharmacology; D025461:Feedback, Physiological / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D020868:Gene Silencing; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D050880:p300-CBP Transcription Factors / Q000378:metabolism
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C524940:MIRN21 microRNA, human; C531950:MIRN21 microRNA, mouse; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; D003035:Cobalt; D050880:p300-CBP Transcription Factors; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C018021:cobaltous chloride
keywords: Cardiomyocytes; Hypoxia; Hypoxia-inducible factor 1α (HIF-1α); MicroRNA; miR-21