MYST4 (also called MORF and KAT6B) is one of the histone acetyltransferases with transcriptional regulatory activity. It was found to be overexpressed in ovarian cancer by a serial analysis of gene expression assays that focused on plant homeodomain-linked domain-containing genes. Compared to ovarian clear cell carcinomas and endometrioid carcinomas, MYST4 is significantly overexpressed in ovarian high-grade serous carcinomas (HGSCs) and was correlated with diminished patient survival in advanced stage HGSCs. Due to limited data on MYST4 in tumorigenesis and tumor progression, we explored the functional roles of MYST4 in human tumors. Besides the ovarian cancer cell line A2780, we chose two other types of human cancer cell lines expressing high mRNA levels of MYST4, SKBR3 and Huh7, for further in vitro investigation. Athymic nu/nu mice were utilized to facilitate the in vivo xenograft study. To search for potentially regulated genes, a microarray study comparing the expression profile before and after MYST4 knockdown was performed. Overexpression of MYST4 in HCCs was significantly associated with decreased survival. The knockdown of MYST4 significantly reduced cellular proliferation, migration, and cell cycle progression in all three cancer cell lines. Moreover, the knockdown of MYST4 in Huh7 cells suppressed tumor growth in a mouse xenograft model. Furthermore, based on our microarray study, we identified several downstream genes important in regulating tumor behaviors. Collectively, our results suggest that MYST4 is involved in cancer progression and contributes to a more aggressive behavior in human solid tumors. Targeting MYST4 represents an appealing strategy for the effective treatment of advanced solid tumors overexpressing MYST4.
Keywords: MYST4; histone acetyltransferase; tumor progression.
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