Integrated analysis of miRNA-mRNA regulatory network and functional verification of miR-338-3p in coronary heart disease

Abstract

Coronary heart disease is a cardiovascular disease with high morbidity and mortality. Although great progress has been made in treatment, the prognosis is still very poor. Therefore, this project aims to identify and screen potential diagnostic markers and therapeutic targets related to the progression of coronary heart disease. A total of 94 overlapping differentially expressed mRNAs and 73 differentially expressed miRNAs were identified by limma package from GSE20681, GSE12288, GSE49823 and GSE105449. Through a series of bioinformatics techniques and qPCR, we obtained 5 core miRNA-mRNA regulatory pairs, and selected miR-338-3p/RPS23 for functional analysis. Moreover, we found that RPS23 directly targets miR-338-3p by dual luciferase assay, western and qPCR. And the expression of miR-338-3p and RPS23 is negatively correlated. The AUC value of miR-338-3p is 0.847. Down-regulation of miR-338-3p can significantly inhibit the proliferation and migration of HUVEC. On the contrary, overexpression of miR-338-3p inhibited HUVEC cell apoptosis and promoted the proliferation and migration of HUVEC. In addition, overexpression of RPS23 can reverse the effect of miR-338-3p mimic on the proliferation activity of HUVECs. Overexpression of miR-338-3p significantly promotes the growth of HUVECs by down-regulating RPS23. In conclusion. The effect of miR-338-3p/RPS23 may be involved in the progression of coronary heart disease, and suggests that miR-338-3p may be a diagnostic biomarker and therapeutic target for coronary heart disease.