LncRNA PEAMIR inhibits apoptosis and inflammatory response in PM2.5 exposure aggravated myocardial ischemia/reperfusion injury as a competing endogenous RNA of miR-29b-3p
Yinghao Pei, Jie Chen, Xiang Wu, Yun He, Wei Qin, Shuyin He, Ning Chang, Hua Jiang, Jiang Zhou, Peng Yu, Haibo Shi, Xiaohu Chen
Abstract
The sensitivity of myocardium is enhanced to ischemia/reperfusion (I/R) injury under PM2.5 exposure. It is still under prelude for lncRNA-miRNA pair in the study of aggravated myocardial I/R injury under PM2.5 exposure. In this study, we first built a rat model of 30 min ischemia and 24 h reperfusion followed PM2.5 (6.0 mg/kg) exposure. We found PM2.5 exposure could obviously aggravate I/R injury in the fields of myocardium damage, apoptosis levels and cardiac function which were evaluated by TTC staining, TUNEL and echocardiography, respectively. Then, based on results of sequencing and RT-qPCR, we selected NONRATT003473.2 in the follow-up experiments and named this lncRNA as PM2.5 exposure aggravated myocardial I/R injury lncRNA (PEAMIR). Consistent with the results rat model, we confirmed PEAMIR to be a protective lncRNA against PM + HR triggered damages in H9c2 cells. Next, according to the bioinformatics analysis from miRanda database and a series of gain- and loss-of-function experiments, we proved PEAMIR to be a ceRNA for miR-29b-3p to inhibit cardiac inflammation and apoptosis. Finally, using Target-Scan database, the conserved binding sites for miR-29b-3p was identified in the 3'UTR of PI3K (p85a), a key protein of apoptosis. Our subsequent experiments validated the regulatory relationship between PEAMIR-miR-29b-3p ceRNA pair and PI3K (p85a)/Akt/GSK3b/p53 cascade pathway. In conclusion, our study demonstrated the role and mechanism of PEAMIR in the augment of I/R injury under PM2.5 exposure, suggesting a promising strategy for the prevention and treatment of I/R injury under PM2.5 exposure.