SIN3B promotes integrin αV subunit gene transcription and cell migration of hepatocellular carcinoma
SIN3B 支持 integrin V 子单元基因抄写和 hepatocellular 癌的房间移植作者机构：Department of Biochemistry and Molecular Biology School of Basic Medical Sciences Fudan University. Key Lab of Glycoconjugate Research Ministry of Public Health Shanghai 200032 China Zhejiang Provincial People's Hospital Hangzhou 310053 China
出 版 物：《Journal of Molecular Cell Biology》 (分子细胞生物学报（英文版）)
年 卷 期：2019年第11卷第5期
页 面：421-432页
核心收录：
学科分类：0710[理学-生物学] 071001[理学-植物学] 07[理学]
基 金：国家自然科学基金
主 题：paired amphipathic helix protein ITGAV sulfatide HCC histone deacetylation
摘 要：Paired amphipathic helix protein (SIN3B) is a transcription corepressor for many genes. Here we show a different regulation mechanism of integrin aV gene expression by SIN3B in human hepatocellular carcinoma (HCC). We first observed a close relationship between Integrin aV and SIN3B expressions in HCC patients and tumor cell lines with different metastatic potentials. Overexpression of SIN3B significantly accelerated the cell migration rate of SMMC-7721, but failed when integrin αV expression was silenced. Interestingly, SIN3B stimulated integrin aV subunit promoter activity only in the presence of sulfatide. Importantly, SIN3B was identified in the complex with sulfatide by mass spectrometry. Fat blot assay indicated that SIN3B specifically interacted with sulfatide. Molecular modeling suggested that sulfatide induced the conformational change of SIN3B from compacted α-helices to a relaxed β-sheet in PAH2 domain. The data of immunoprecipitation and ChIP assay indicated that altered SIN3B lost the binding affinity with MAD1 and HDAC2, which reduced the recruitment of HDAC2 on integrin aV gene promoter and prevented the deacetylation of the histone 3. In conclusion, this study demonstrated that SIN3B promoted the transcriptional activation of the integrin αV subunit gene promoter by reducing interaction with HDAC2.
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