Integrated Bioinformatic Analysis of miRNA–Gene interactions in Lipid Metabolism and Atherosclerosis

Abstract

Atherosclerosis is a leading global cause of cardiovascular death and mortality. The development of atherogenesis involves abnormal lipid metabolism, endothelial dysfunction, chronic inflammation and excessive proliferation of vascular smooth muscle cells. MicroRNAs (miRNAs) are small non-coding RNAs that regulate post transcriptional gene expression. This study aims to identify the overexpressed miRNAs in atherosclerosis to characterize their regulatory interactions with genes involved in cholesterol homeostasis and lipid metabolism, thereby evaluating their potential as novel biomarker and therapeutic agent. Three proatherogenicmiRNAs: hsa-miR-128-3p, hsa-miR-130a3p and hsa-miR-17-5p were identified based on their association with key cholesterol-regulating genes, including LDLR, ABCA1, ABCG5 and LRP6. miRNAtarget interactions were experimentally validated using miRTarBase. Functional enrichment and network analyses were performed using MIENTURNET while RNA fold and RNA composer were employed for secondary and three-dimensional structure prediction respectively. Molecular docking studies using HNADOCK assessed binding affinities between selected miRNAs and their target genes. Docking analysis revealed strong binding interactions with miR-128-3p and miR-17-5p primarily targeting LDLR and LRP6, while miR-130a-3p specifically interacted with ABCA1 and ABCG5. These findings highlight distinct high-affinity regulatory roles of miRNAs in cholesterol metabolism and underscore their promise as novel biomarkers and therapeutic targets for early detection and treatment of atherosclerosis.