miR-122 overexpression induces autophagy via PKM2 downregulation in Non-alcoholic fatty liver disease

Background and Aim: Non-alcoholic Fatty Liver Disease (NAFLD) is a significant global health concern, causing chronic liver disease. miR-122, microRNA abundant in the liver, found to be downregulated various cancers, including hepatocellular carcinoma (HCC). PKM2, variant of Pyruvate Kinase (PK), has been implicated HCC development due its high expression tumor tissues. PKM2 overexpression causes inflammation inhibits autophagy apoptosis cancer cells. Since miR-122 targets inhibiting could potentially downregulate NAFLD induce autophagy, making potential target for treatment. Methods: C57BL/6 mice were fed control, choline sufficient L-amino acid (CSAA), or deficient (CDAA) diets. After 6, 18, 32, 54 weeks, euthanized, tissues homogenized analyzed changes markers (Atg7, Beclin-1, LC3B) using RT-PCR Western blotting. HepG2 cells treated with free fatty acids regulation determined. The overexpressing knocked down Results: results mouse model showed that CDAA diet led downregulation expression, upregulation (p<0.05), (p<0.05). In FFAs, was increased, while significantly decreased Overexpressing resulted two-fold (p<0.05) increase markers. Moreover, similar as above. Conclusion: These findings confirmed leads increased enhancing autophagy. This suggests targeting novel approach regulate progression prevent HCC.