KDM6A suppresses hepatocellular carcinoma cell proliferation by negatively regulating the TGF-β/SMAD signaling pathway

Lysine demethylase 6A (KDM6A) is a Jumonji-C domain-containing histone demethylase that specifically catalyzes the removal of histone H3 lysine-27 trimethylation. KDM6A is a member of the KDM6 family, the biological role of which has been reported in various types of cancer, including bladder and lung cancer, as well as pancreatic ductal adenocarcinoma. However, the role of KDM6A in hepatocellular carcinoma (HCC) is not completely understood. Therefore, the present study aimed to determine the biological function of KDM6A in HCC progression. The expression profile of KDM6A was examined in HCC surgical specimens using reverse transcription-quantitative PCR. In addition, the role of KDM6A in the proliferation capacities of HCC cell lines was examined in vitro and in vivo using crystal violet and MTT assays. The underlying mechanism by which KDM6A exerts its function was explored by western blotting. The present study indicated that KDM6A was significantly downregulated in HCC tissues compared with normal control tissues. The role of KDM6A in HCC cell proliferation was also determined. KDM6A overexpression significantly inhibited HCC cell proliferation, whereas KDM6A knockdown significantly promoted HCC cell proliferation compared with the corresponding control groups. Consistently, KDM6A overexpression suppressed HCC cell tumorigenesis in vivo. The western blotting results indicated that KDM6A overexpression decreased the phosphorylation levels of smad2, whereas KDM6A knockdown increased the phosphorylation levels of smad2 compared with the corresponding control groups. Therefore, the present study suggested that KDM6A may inhibit HCC cell proliferation by negatively regulating the TGF-β/SMAD signaling pathway, suggesting that KDM6A may serve as a potential target for the diagnosis and treatment of HCC.