Exploring the function of microRNA-372-3P in lipid metabolism of hepatocellular carcinoma cells

Abstract

Hepatocellular carcinoma (HCC) remains one of the most prevalent and lethal malignancies worldwide, characterized by limited treatment options and a poor prognosis. Emerging evidence underscores the central role of metabolic reprogramming in HCC development, with microRNAs (miRNAs) recognized as key modulators. However, the contribution of miR-372-3p to HCC pathogenesis remains insufficiently explored. This study elucidates the functional and therapeutic significance of miR-372-3p in HCC through transcriptomic profiling and cell-based assays. Enforced expression of miR-372-3p significantly inhibits HCC cell proliferation, migration, invasion, and colony formation. Transcriptomic and gene-set enrichment analyses reveal suppression of fatty acid oxidation (FAO) genes, notably CPT1A and ACSL4, confirmed as direct targets using dual-luciferase reporter assays. Functionally, miR-372-3p overexpression promotes lipid-droplet accumulation and impairs FAO activity under glucose deprivation, accompanied by disrupted interactions between lipid droplets and organelles such as mitochondria and lysosomes. Collectively, these findings establish miR-372-3p as a metabolic tumor suppressor and highlight its promise as a novel therapeutic target in HCC. This work advances understanding of miRNA-mediated metabolic regulation in liver cancer and supports future miRNA-based therapeutic strategies to address persistent gaps in HCC treatment.