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

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Centromere protein F (CENP-F) is overexpressed in hepatocellular carcinoma (HCC).
• The precise mechanism of CENP-F's role in HCC progression remains elusive.
• Super enhancer (SE) readers, including BRD4, CDK1, CDK2, and CDK7, show increased activity in HCC.

Purpose of the Study:

• To elucidate the regulatory mechanism of CENP-F in HCC development.
• To investigate the association between CENP-F and key cell cycle regulators and SE readers in HCC.

Main Methods:

• Bioinformatic analysis.
• In vitro cell experiments using HepG2 and Hep3B cell lines.
• In vivo xenograft tumor models in mice.
• Manipulation of CENP-F and BRD4 expression via knockdown (siRNA) and pharmacological inhibition (JQ1).

Main Results:

• Protein levels of CENP-F, CDK1, CDK2, CDK7, and BRD4 were elevated in HCC tissues.
• CENP-F expression positively correlated with CDK1, CDK2, CDK7, and BRD4.
• CENP-F downregulation inhibited HCC cell proliferation and decreased protein levels of CENP-F, CDK1, CDK2, BRD4, and c-Myc.
• BRD4 knockdown reduced BRD4 and c-Myc protein levels.
• Both CENP-F and BRD4 inhibition suppressed tumor growth in vivo.

Conclusions:

• CENP-F promotes HCC cell proliferation via the CENP-F-CDK1/CDK2-BRD4 signaling axis.
• Super enhancers are crucial mediators in HCC pathogenesis and potential therapeutic targets.