Overexpression of KDM6A in Hepatoma Cells Induces Hepatocytic Differentiation and Attenuates Proliferation Rate, Colony Formation, and Migration Capacities.

Objective: Despite the remarkable advances in approved therapeutic approaches, the recurrence rate of hepatocellular carcinoma (HCC) is very high after treatment. Therefore, introducing innovative therapeutic modalities such as targeted molecular therapies is inevitable. Lysine demethylase 6A (KDM6A) is a member of the KDM6 family with histone demethylase activity. This gene frequently mutates in different cancers, and its mutations are associated with the increased likelihood of carcinogenesis. This study is aimed at evaluating if inducing KDM6A expression could attenuate cancerous features of HCC cells. Method: A lentiviral-based vector was used to induce KDM6A expression in Huh-7 cells. The impact of KDM6A overexpression on the cancerous phenotype of HCC cells was assessed by measuring proliferation rate, migration and colony formation capacity, and differentiation induction toward hepatocytes. Results: KDM6A overexpression significantly altered cellular morphology, proliferation rate, cell cycle pattern, colony formation, and migration capacity of HCC cells. In addition, induction of differentiation toward hepatocytic fate resulted in down/upregulation of epithelial-mesenchymal transition (EMT) markers associated with the cadherin switch. Furthermore, the expressions of ALB and HNF4α, key hepatocytic hallmarks, were increased. Conclusion: Overexpression of KDM6A could be used as a potential noninvasive molecular therapeutic strategy to prevent metastasis and recurrence rate in HCC.