Circular RNA_101237 mediates anoxia/reoxygenation injury by targeting let-7a-5p/IGF2BP3 in cardiomyocytes
Circular RNA_101237 mediates anoxia/reoxygenation injury by targeting let-7a-5p/IGF2BP3 in cardiomyocytes
复制标题
环状RNA_101237通过靶向let-7a-5p/IGF2BP3介导心肌细胞缺氧/复氧损伤
DOI：
10.3892/ijmm.2019.4441
复制
发表时间：
2020-02-01
影响因子：
5.4
通讯作者：
Zeng, Huayuan
中科院分区：
文献类型：
--
作者：
Gan, Jianting;Yuan, Jun;Zeng, Huayuan
环状RNA（circRNA）在包括心肌梗死在内的心血管疾病中发挥重要作用。然而，circRNA在缺氧/复氧（A/R）诱导的心肌细胞死亡中的作用机制尚不完全清楚。在本研究中，研究了circRNA_101237和let-7a-5 p在A/R损伤诱导的心肌细胞死亡中的作用。已确定circRNA_101237以时间依赖性方式由A/R损伤诱导，并且circRNA_101237敲低保护心肌细胞免于A/R介导的凋亡。额外的机制研究表明，circRNA_101237充当let-7a-5 p的海绵，随后调节胰岛素样生长因子2 mRNA结合蛋白3（IGF 2BP 3）依赖性自噬。IGF 2BP 3下调可降低A/R刺激诱导的原代心肌细胞凋亡水平，抑制自噬。这些结果将circRNA_101237鉴定为调节心肌细胞死亡和自噬的新型circRNA，并证明作为心肌细胞死亡调节剂的circRNA-101237/let-7a-5 p/IGF 2BP 3轴可能是心血管疾病管理的潜在治疗靶点。
Circular RNAs (circRNAs) serve important roles in cardiovascular diseases, including myocardial infarction. However, the mechanisms underlying the roles of circRNAs in cardiomyocyte death induced by anoxia/reoxygenation (A/R) are not fully understood. In the present study, the roles of circRNA_101237 and let-7a-5p in cardiomyocyte death induced by A/R injury were investigated. It was identified that circRNA_101237 was induced by A/R injury in a time-dependent manner and that circRNA_101237 knockdown protected cardiomyocytes from A/R-mediated apoptosis. Additional mechanistic studies revealed that circRNA_101237 served as a sponge for let-7a-5p, subsequently regulating insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3)-dependent autophagy. IGF2BP3 downregulation decreased the levels of apoptosis and inhibited autophagy induced by A/R challenge in primary cardiomyocytes. These results identified circRNA_101237 as a novel circRNA that regulates cardiomyocyte death and autophagy, and demonstrated that the circRNA-101237/let-7a-5p/IGF2BP3 axis, which serves as a regulator of cardiomyocyte death, may be a potential therapeutic target for the management of cardiovascular diseases.