Open AccessFOXO3a‐mediated long non‐coding RNA LINC00261 resists cardiomyocyte hypoxia/reoxygenation injury via targeting miR23b‐3p/NRF2 axis
Author(s) -
Zhang Ruining,
Li Yongjun,
Liu Xiaopeng,
Qin Shan,
Guo Bingyan,
Chang Liang,
Huang Liu,
Liu Suyun
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15292
Subject(s) - chromatin immunoprecipitation , transcription factor , biology , apoptosis , microbiology and biotechnology , long non coding rna , hypoxia (environmental) , transcription (linguistics) , downregulation and upregulation , cancer research , gene expression , chemistry , gene , biochemistry , promoter , linguistics , organic chemistry , philosophy , oxygen
Ischemia/reperfusion (I/R)‐mediated acute myocardial infarction (AMI) is a major pathological factor implicated in the progression of ischemic heart disease (IHD). Long non‐coding RNA plays an important role in regulating the occurrence and development of cardiovascular disease. The aim of this study was to investigate the regulating role of LINC00261 in hypoxia/reoxygenation (H/R)‐induced cardiomyocyte apoptosis. The relative expression of LINC00261, miR‐23b‐3p and NRF2 were determined in rats I/R myocardial tissues and H/R‐induced cardiomyocytes. The rat model and cell model of LINC00261 overexpression were established to investigate the biological function of LINC00261 on H9C2 cell. The interaction between LINC00261, miR‐23b‐3p, NRF2 and FOXO3a was identified using bioinformatics analysis, luciferase reporter assay, RNA immunoprecipitation (RIP) assay, chromatin immunoprecipitation (CHIP) assay and qRT‐PCR. The expression of LINC00261 was significantly down‐regulated in myocardial tissues and H9C2 cell. Overexpression of LINC00261 improves cardiac function and reduces myocardium apoptosis. Interestingly, transcription factor FOXO3a was found to promote LINC00261 transcription. Moreover, LINC00261 was confirmed as a spong of miR23b‐3p and thereby positively regulates NRF2 expression in cardiomyocytes. Our findings reveal a novel role for LINC00261 in regulating H/R cardiomyocyte apoptosis and the potency of the LINC00261/miR‐23b‐3p/NRF2 axis as a therapeutic target for the treatment of MIRI.