Shi Meijing, Ma Xiuru, Yang Qian, Wang Wenjing, Li Xinning, Song Xuelian, Li Yingxiao, Xie Yuetao, Dang Yi
School of Graduate, Hebei Medical University, Shijiazhuang, Hebei, 050017, P.R. China.
College of Integrated Chinese and Western Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, P.R. China.
Cardiovasc Toxicol. 2021 May;21(5):387-398. doi: 10.1007/s12012-020-09631-0. Epub 2021 Jan 18.
This study aimed to investigate the mechanism of how miR-362-3p/orosomucoid 1 (ORM1) involved in hypoxia/reoxygenation (H/R)-induced cardiomyocytes injury. Based on data obtained from Gene Expression Omnibus (GEO) database, we revealed that ORM1 was highly expressed and positively correlated with the expression of inflammatory factors (MAPK1, MAPK3, IL1B and CASP9). miR-362-3p was identified as an upstream regulatory miRNA of ORM1 and negatively modulated the mRNA and protein expression levels of ORM1 in H/R-injured cardiomyocytes. Moreover, we found that miR-362-3p was downregulated in cardiomyocytes injured by H/R. The promoting influence of miR-362-3p mimic on the proliferation and the inhibitory effect of miR-362-3p mimic on the apoptosis of H/R-stimulated cardiomyocytes were eliminated by overexpression of ORM1. Furthermore, miR-362-3p affected the expression of MAPK1, MAPK3, IL1B and CASP9 in H/R-injured cardiomyocytes through targeting ORM1. Our outcomes illustrated that miR-362-3p exhibited a protective influence on H/R-induced cardiomyocytes through targeting ORM1.
本研究旨在探究miR-362-3p/血清类黏蛋白1（ORM1）参与缺氧/复氧（H/R）诱导的心肌细胞损伤的机制。基于从基因表达综合数据库（GEO）获得的数据，我们发现ORM1高表达且与炎症因子（MAPK1、MAPK3、IL1B和CASP9）的表达呈正相关。miR-362-3p被鉴定为ORM1的上游调控miRNA，并在H/R损伤的心肌细胞中负向调节ORM1的mRNA和蛋白表达水平。此外，我们发现miR-362-3p在H/R损伤的心肌细胞中表达下调。过表达ORM1消除了miR-362-3p模拟物对H/R刺激的心肌细胞增殖的促进作用以及对其凋亡的抑制作用。此外，miR-362-3p通过靶向ORM1影响H/R损伤的心肌细胞中MAPK1、MAPK3、IL1B和CASP9的表达。我们的结果表明，miR-通过靶向ORM1对H/R诱导的心肌细胞发挥保护作用。
