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

• Published in: Nanotoxicology 2020-05, Vol.14 (5), p.638-653
• Main Authors: Pei, Ying-Hao, Chen, Jie, Wu, Xiang, He, Yun, Qin, Wei, He, Shu-Yin, Chang, Ning, Jiang, Hua, Zhou, Jiang, Yu, Peng, Shi, Hai-Bo, Chen, Xiao-Hu
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Apoptosis; Binding sites; Bioinformatics; ceRNA; Damage; Data bases; Echocardiography; Experiments; Exposure; Heart; I/R injury; Inflammation; Inflammatory response; Injury prevention; Ischemia; LncRNA PEAMIR; miR-29b-3p; miRNA; Myocardial ischemia; Myocardium; p53 Protein; Particulate matter; PM2.5 exposure; Reperfusion; Sensitivity enhancement; Sequences
• ISSN: 1743-5390; 1743-5404
• DOI: 10.1080/17435390.2020.1731857

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.