Department of Cardiovascular Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang Province, China.
Department of Cardiovascular Medicine, Lianyungang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Lianyungang, Jiangsu Province, China.
J Biochem Mol Toxicol. 2021 Apr;35(4):e22709. doi: 10.1002/jbt.22709. Epub 2021 Jan 24.
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.
心肌缺血/再灌注（I/R）损伤是一种非常常见的心血管疾病，也是死亡的主要原因之一。大量证据表明，长链非编码 RNA（lncRNA）在心肌 I/R 损伤中起着至关重要的作用。lncRNA 心脏肥大相关因子（CHRF）已被揭示为心脏疾病的重要调节剂。然而，CHRF 在心肌 I/R 损伤中的功能尚不清楚。在我们目前的工作中，我们发现 CHRF 的表达在心肌 I/R 损伤模型中上调。抑制 CHRF 缓解了体内心肌 I/R 损伤。此外，体外沉默 CHRF 增强了 H9C2 细胞在缺氧/复氧损伤中的细胞活力，并减弱了乳酸脱氢酶（LDH）活性和细胞凋亡。自噬已被研究在心肌 I/R 损伤中发挥重要作用。因此，进行了与自噬相关的实验，结果表明 CHRF 敲低减少了自噬。为了探索调节机制，我们发现 CHRF 隔离并负调控 miR-182-5p，从而释放其对 ATG7 的抑制作用。挽救实验的结果表明，ATG7 的过表达可以抑制 CHRF 沉默对细胞活力、LDH 水平、细胞凋亡和自噬的影响。总之，我们的研究结果表明，CHRF 通过调节 miR-182-5p/ATG7 通路增强自噬从而加剧心肌 I/R 损伤。因此，这种竞争性内源性 RNA 轴可能是心肌 I/R 损伤的潜在治疗生物标志物。
