EYA4 inhibits hepatocellular carcinoma by repressing MYCBP by dephosphorylating β-catenin at Ser552

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Hepatocellular carcinoma (HCC) is a leading cause of cancer death globally.
• The precise molecular mechanisms by which EYA4 suppresses HCC tumor growth remain unclear.
• Previous research indicated EYA4's tumor-suppressive role in HCC.

Purpose of the Study:

• To elucidate the molecular mechanism of EYA4 in suppressing HCC tumor cell growth.
• To investigate the relationship between EYA4 and MYCBP in HCC.
• To evaluate EYA4 and MYCBP as potential prognostic biomarkers for HCC.

Main Methods:

• Gene microassay, immunohistochemistry, and western blot to assess EYA4 and MYCBP correlation.
• Quantitative real-time PCR (qRT-PCR) and western blot to confirm gene expression changes.
• Functional assays involving gene overexpression and knockout (KO) in HCC cell lines, including siRNA transfection.

Main Results:

• EYA4 expression was inversely correlated with MYCBP expression in HCC tissues and cell lines.
• EYA4 dephosphorylates beta-catenin at Ser552, reducing its nuclear translocation.
• This dephosphorylation inhibits beta-catenin/LEF1-induced MYCBP transcription, suppressing HCC cell proliferation and G2/M arrest.
• High EYA4 and low MYCBP expression correlated with significantly better patient survival outcomes.

Conclusions:

• EYA4 suppresses HCC tumor growth by inhibiting MYCBP expression via dephosphorylation of beta-catenin at Ser552.
• The EYA4/MYCBP axis represents a novel therapeutic target and potential prognostic biomarker in HCC.
• Understanding this pathway provides insights into HCC progression and potential treatment strategies.