MicroRNA-Mediated Post-Transcriptional Regulation of Lipid Metabolism Genes in Patients with Non-Alcoholic Steatohepatitis in South South Nigeria

Non-alcoholic steatohepatitis represents the inflammatory and fibrotic progression of non-alcoholic fatty liver disease, and dysregulated microRNAs controlling hepatic lipid metabolism genes are emerging as central players in this transition. This study characterises the hepatic and circulating microRNA expression profiles associated with non-alcoholic steatohepatitis, focusing on miR-122, miR-34a, miR-21, and miR-155 as regulators of lipogenesis and fatty acid oxidation genes in patients in Rivers and Delta States, South South Nigeria. A case-control design was employed, with 60 biopsy-confirmed NASH patients, 60 simple steatosis patients, and 60 healthy controls. Plasma microRNA profiling was performed by next-generation small RNA sequencing, and candidate miRNA expression was validated by quantitative RT-PCR. Target gene expression, specifically PPAR-alpha, SREBP-1c, and FASN mRNA, was measured in liver biopsy tissue. Luciferase reporter assays validated the direct post-transcriptional interactions between selected miRNAs and target gene 3-prime UTR regions. A novel miRNA-lipid metabolism gene interaction network was constructed using Cytoscape. This study generates an original theoretical contribution to understanding miRNA regulation of hepatic lipid metabolism in NASH and identifies candidate circulating miRNA biomarkers applicable to non-invasive NASH diagnosis. Keywords: microRNA, non-alcoholic steatohepatitis, lipid metabolism, miR-122, South South Nigeria.