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

Abstract

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.

Dexmedetomidine promotes cell proliferation and inhibits cell apoptosis by regulating LINC00982 and activating the phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT) signaling in hypoxia/reoxygenation-induced H9c2 cells

“…For instance, Liu et al reported that SNHG7 deletion repressed H/R-induced cardiomyocyte oxidative stress and apoptosis via increasing miR-181b-5p expression, thereby exerting a protective effect on cardiomyocytes [ 21 ]. Mo et al displayed that lncRNA CHRF was upregulated in MIRI, and CHRF silencing could relieve MIRI by attenuating myocardial cell apoptosis [ 22 ]. Xu et al elaborated that LINC00982 addition could promote cell apoptosis through modulating PI3K/AKT signaling in papillary thyroid carcinoma [ 23 ].…”

The role and medical prospects of long non-coding RNAs in cardiovascular disease

“…In the context of myocardial I/R injury, silencing of Chrf reduces autophagy, inhibits apoptosis, increases cell viability, and reduces lactate dehydrogenase (LDH) levels. Chrf appears to limit myocardial I/R injury by preventing Atg7 from being inhibited by miR-182-5p [ 23 ].…”

LncRNA-POIR knockdown promotes hepatocellular carcinoma sensitivity to sorafenib through upregulating miR-182-5p and inhibiting autophagy

“…The previous study has shown that miR-182-5p is the downstream target of POIR (Wang et al, 2016). MiR-182-5p has also been shown to regulate autophagy in other diseases (Mo et al, 2021;Xie et al, 2019). However, it is not clear whether POIR regulates autophagy in HCC by regulating miR-182-5p.…”