JMJD6 promotes hepatocellular carcinoma carcinogenesis by targeting CDK4.

Abstract

Jumonji domain-containing protein 6 (JMJD6), a histone arginine demethylase, plays a multifaceted and significant role in embryonic development and cancer progression. However, the function of JMJD6 and its precise mechanism in regulating hepatocellular carcinoma (HCC) remain unknown. Here, we show that aberrant JMJD6 overexpression is associated with poor prognosis and aggressive characteristics of HCC. In hepatoma cell lines, we demonstrated that knockdown of JMJD6 inhibited hepatoma cell migration and proliferation. JMJD6 overexpression displays the opposite effects. Interestingly, JMJD6 regulates hepatoma cell cycle and apoptosis progression. Moreover, there was a positive correlation between cell cycle regulatory protein CDK4 and JMJD6 level. Mechanism analysis suggested JMJD6 promotes CDK4 expression by directly targeting to its promoter, and interacts with PCAF to regulate the histone modifications on the promoter of CDK4. Furthermore, we found that inhibiting CDK4 abolished the ability of JMJD6 in enhancing cell proliferation. Taken together, for the first, we demonstrated that JMJD6 is critically involved in HCC carcinogenesis, and indicated that JMJD6 may be a novel potential biomarker for HCC.