Abstract
The purpose of this study was to reveal the hypothesis that lncRNA X inactive specific transcript (XIST) can participate in the regulation of cardiomyocyte apoptosis in neonatal mice cardiomyocytes (NMCMs) and myocardial infarction (MI) through targeting miR-101a-3p. NMCMs were isolated from neonatal C57BL/6 mice and anoxia was induced in hypoxic chamber. MTT assay and flow cytometry were used to determine proliferation and apoptosis respectively. The target relationship among XIST, miR-101a-3p and FOS was revealed by bioinformatic analysis, luciferase reporter assay, pull-down assay and RNA immunoprecipitation assay. The expression of XIST, miR-101a-3p, FOS and apoptosis-related proteins was determined by qRT-PCR or western blot. MI model was constructed to reveal the role of XIST. We found that XIST was up-regulated in NMCMs under anoxia condition. Moreover, XIST increased FOS expression by sponging miR-101a-3p in anoxia cells. Silencing XIST expression improved cell viability and suppressed apoptosis in vitro and inhibited myocardial infarction by reducing the level of c-FOS and apoptosis-related proteins in vivo. Our findings suggest that XIST is involved in MI, modulation of its level can be used as a new strategy or potential target in the treatment of myocardial infarction.
Highlights
Coronary heart disease (CHD), called coronary artery disease (CAD) [1], is the shortened name of coronary atherosclerotic heart disease
The present study established that the lncRNA X inactive specific transcript (XIST) was a damaging factor in myocardial infarction (MI), whereas miR-101a-3p was a protective miRNA in MI
We proved that knocking down of XIST significantly improved the cell viability and decreased apoptosis rate under anoxia, and our results showed that the mice treated with XIST-small mice interfering RNA (siRNA) adenoviruses exhibited a significant reduction in myocardial infarction sizes and the expression of apoptosis-related proteins
Summary
Coronary heart disease (CHD), called coronary artery disease (CAD) [1], is the shortened name of coronary atherosclerotic heart disease. CHD is a common chronic disease, which is mainly is mainly due to the gradual constriction of the blood vessels that supply oxygenated blood to the myocardium [2]. Coronary heart disease includes a group of diseases, including myocardial infarction (MI), unstable angina, stable angina and sudden cardiac death [3]. MI is the material cause of mortality in CHD patients, it is the leading global cause of death, especially in China, and its incidence and fatality rate have increased [4]. With the progress of genetic sequencing, an increasing number of disease-related genes have been found, which will help people understand the relationship between genes and diseases [6, 7]
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