CENP-F promotes HCC cell proliferation mediated by super enhancer reader BRD4

Centromere protein F (CENP-F) is highly expressed in hepatocellular carcinoma (HCC), but the specific mechanism by which it regulates the occurrence and development of HCC is currently unclear. The activities of the super enhancer (SE) readers bromodomain-containing protein 4 (BRD4), cyclin-dependent kinase 1 (CDK1), cyclin-dependent kinase 2 (CDK2) and cyclin-dependent kinase 7 (CDK7) are significantly increased in HCC. This study explored the mechanism of CENP-F regulation in HCC through bioinformatics and cell and animal experiments. We found that the protein levels of CENP-F, CDK1, CDK2, CDK7 and BRD4 were significantly increased in HCC and that CENP-F was closely associated with CDK1, CDK2, CDK7 and BRD4. Downregulation of CENP-F led to a decrease in the protein levels of CENP-F, CDK1, CDK2, BRD4 and c-Myc and inhibited the proliferation of HepG2 and Hep3B cells. After overexpression of CENP-F, the above parameters returned to their previous levels. In addition, downregulation of BRD4 using siRNA and JQ1 led to decreases in the protein levels of BRD4 and c-Myc. CENP-F or BRD4 knockdown inhibited xenograft tumor growth in an in vivo HCC model. These findings suggested that CENP-F regulated the proliferation of HCC cells through the CENP-F-CDK1/CDK2-BRD4 axis. In conclusion, our study revealed a new mechanism by which CENP-F promotes HCC cell proliferation by the SE reader BRD4, suggesting that SEs play an essential role in mediating HCC treatment.