RNA-SEQ ANALYSIS OF HUMAN NEURONS DERIVED FROM INDUCED PLURIPOTENT STEM CELLS CONTAINING A KNOCKOUT OF THE AUTISM AND SCHIZOPHRENIA CANDIDATE GENE CHD8 (CHROMODOMAIN-HELICASE-DNA-BINDING PROTEIN)
EUROPEAN NEUROPSYCHOPHARMACOLOGY
Authors: Wang, Ping; Lin, Mingyan; Pedrosa, Erika; Hrabovsky, Anastasia; Guo, Wenjun; Zhang, Zheng; Zheng, Deyou; Lachman, Herb
Abstract
Critical roles of microRNA-141-3p and CHD8 in hypoxia/reoxygenation-induced cardiomyocyte apoptosis
CELL AND BIOSCIENCE
Authors: Yao, Bifeng; Wan, Xiaoya; Zheng, Xinbin; Zhong, Ting; Hu, Jia; Zhou, Yu; Qin, Anna; Ma, Yeshuo; Yin, Deling
Abstract
Background Cardiovascular diseases are currently the leading cause of death in humans. The high mortality of cardiac diseases is associated with myocardial ischemia and reperfusion (I/R). Recent studies have reported that microRNAs (miRNAs) play important roles in cell apoptosis. However, it is not known yet whether miR-141-3p contributes to the regulation of cardiomyocyte apoptosis. It has been well established that in vitro hypoxia/reoxygenation (H/R) model can follow in vivo myocardial I/R injury. This study aimed to investigate the effects of miR-141-3p and CHD8 on cardiomyocyte apoptosis following H/R. Results We found that H/R remarkably reduces the expression of miR-141-3p but enhances CHD8 expression both in mRNA and protein in H9c2 cardiomyocytes. We also found either overexpression of miR-141-3p by transfection of miR-141-3p mimics or inhibition of CHD8 by transfection of small interfering RNA (siRNA) significantly decrease cardiomyocyte apoptosis induced by H/R. Moreover, miR-141-3p interacts with CHD8. Furthermore, miR-141-3p and CHD8 reduce the expression of p21. Conclusion MiR-141-3p and CHD8 play critical roles in cardiomyocyte apoptosis induced by H/R. These studies suggest that miR-141-3p and CHD8 mediated cardiomyocyte apoptosis may offer a novel therapeutic strategy against myocardial I/R injury-induced cardiovascular diseases.
COA
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