Regulatory effects of miR-30c knockout on hepatic lipid metabolism and progression of liver fibrosis

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BACKGROUND: Liver fibrosis is a chronic progressive liver disease influenced by environmental and genetic factors. Early stages of liver fibrosis are marked by abnormal fat deposition in the liver. MicroRNA-30c (miR-30c) plays key roles in various pathological processes, including lipid metabolism, metabolic disorders, and cancer. However, the precise role of miR-30c in the progression of liver fibrosis remains unclear. This study aimed to investigate the role of miR-30c in liver fibrosis using miR-30c knockout (KO) mice. METHODS: KO mice were compared to wild-type (WT) mice to evaluate growth and development, with a focus on lipid metabolism markers. Liver transcriptomic analysis was performed to explore gene expression alterations due to miR-30c knockout. To induce liver fibrosis, thioacetamide (TAA) was administered to the mice, allowing the assessment of the impact of miR-30c on fibrosis initiation and progression. RESULTS: The results showed that miR-30c knockout led to body weight loss and disrupted lipid metabolism in mice. A total of 212 upregulated genes and 267 downregulated genes were identified in the livers of KO mice by RNA-seq. Differential enrichment of lipid metabolism pathways was observed KO mice, including PPAR signaling pathway, fatty acid degradation, biosynthesis of unsaturated fatty acids, and so on. The deletion of miR-30c aggravated the liver injury induced by TAA and increased the structural disorder of hepatocytes, and miR-30c knockout mice showed more severe liver fibrosis. This study establishes miR-30c as protective against liver fibrosis progression. CONCLUSION: The deficiency of miR-30c might exacerbate fibrosis and inflammation, while also disrupting lipid metabolism, suggesting that miR-30c modulation shows therapeutic potential based on mechanistic evidence. Further exploration of miR-30c-mediated crosstalk between metabolic and inflammatory pathways could advance therapeutic strategies for fibrotic liver diseases.