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

Cancer Science
Xiao-Xu ZhuXiao-Yu Yin

Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignancies and the fourth leading cause of cancer-related death worldwide. Our previous study showed that EYA4 functioned by suppressing growth of HCC tumor cells, but its molecular mechanism is still not elucidated. Based on the results of gene microassay, EYA4 was inversely correlated with MYCBP and was verified in human HCC tissues by immunohistochemistry and western blot. Overexpressed and KO EYA4 in human HCC cell lines confirmed the negative correlation between EYA4 and MYCBP by qRT-PCR and western blot. Transfected siRNA of MYCBP in EYA4 overexpressed cells and overexpressed MYCBP in EYA4 KO cells could efficiently rescue the proliferation and G2/M arrest effects of EYA4 on HCC cells. Mechanistically, armed with serine/threonine-specific protein phosphatase activity, EYA4 reduced nuclear translocation of β-catenin by dephosphorylating β-catenin at Ser552, thereby suppressing the transcription of MYCBP which was induced by β-catenin/LEF1 binding to the promoter of MYCBP. Clinically, HCC patients with highly expressed EYA4 and poorly expressed MYCBP had significantly longer disease-free survival and overall survival than HCC patients with poorly expressed EYA4 and ...Continue Reading

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Citations

Jun 19, 2020·Experimental Hematology & Oncology·Bing DongKongming Wu

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Datasets Mentioned

BETA
GSE45436
GSE14520

Methods Mentioned

BETA
surgical resection
PCR
transfection
nuclear translocation

Software Mentioned

ImageJ
SPSS
ZEN
GEPIA
FlowJo

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