Myocardial Ischamia Reperfusion Injury Injury

CHRF[LncRNA]

miR-182-5p[miRNA]

ATG7[mRNA]

H9C2 cells

Homo sapiens (human)

J Biochem Mol Toxicol. 2021 Apr;35(4):e22709. doi: 10.1002/jbt.22709. Epub 2021 Jan 24.

LncRNA CHRF aggravates myocardial ischemia/reperfusion injury by enhancing autophagy via modulation of the miR-182-5p/ATG7 pathway.

Rescue assay;

Myocardial ischemia/reperfusion (I/R) injury is a very frequent cardiovascular disease and one of the leading causes of death. Abundant evidence has shown that long noncoding RNAs (lncRNAs) are crucial players in myocardial I/R injury. LncRNA cardiac hypertrophy-related factor (CHRF) has been revealed as an important modulator in cardiac disease. However, the function of CHRF in myocardial I/R injury is unclear. In our current work, we found that the expression of CHRF was upregulated in myocardial I/R injury models. Suppression of CHRF relieved myocardial I/R injury in vivo. In addition, in vitro silencing of CHRF enhanced cell viability and attenuated lactate dehydrogenase activity (LDH) as well as apoptosis in H9C2 cells treated with hypoxia/reoxygenation injury. Autophagy has been studied to play an important role in myocardial I/R injury. Thus, experiments related to autophagy were done, and the results showed that CHRF knockdown decreased autophagy. For the exploration of the regulatory mechanism, we found that CHRF sequestered and negatively regulated miR-182-5p to release its inhibition on ATG7. Findings from rescue assays revealed that ATG7 overexpression could suppress the effects of CHRF silence on cell viability, LDH level, apoptosis, and autophagy. To sum up, our results suggested that CHRF exacerbated myocardial I/R injury by enhancing autophagy via modulation of the miR-182-5p/ATG7 pathway. Therefore, this competing endogenous RNA axis may be a potential therapeutic biomarker for myocardial I/R injury.