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SIN3B promotes integrin ?V subunit gene transcription and cell migration of hepatocellular carcinoma.


ABSTRACT: Paired amphipathic helix protein (SIN3B) is a transcription corepressor for many genes. Here we show a different regulation mechanism of integrin ?V gene expression by SIN3B in human hepatocellular carcinoma (HCC). We first observed a close relationship between Integrin ?V 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 ?V expression was silenced. Interestingly, SIN3B stimulated integrin ?V 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 ?-helices to a relaxed ?-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 ?V gene promoter and prevented the deacetylation of the histone 3. In conclusion, this study demonstrated that SIN3B promoted the transcriptional activation of the integrin ?V subunit gene promoter by reducing interaction with HDAC2.

SUBMITTER: Cai Q 

PROVIDER: S-EPMC7727265 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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SIN3B promotes integrin αV subunit gene transcription and cell migration of hepatocellular carcinoma.

Cai Qianqian Q   Liu Yuanyuan Y   Zhu Ping P   Kang Chunlang C   Xu Heyang H   Qi Bing B   Wang Rong R   Dong Yiwei Y   Wu Xing Zhong XZ  

Journal of molecular cell biology 20190501 5


Paired amphipathic helix protein (SIN3B) is a transcription corepressor for many genes. Here we show a different regulation mechanism of integrin αV gene expression by SIN3B in human hepatocellular carcinoma (HCC). We first observed a close relationship between Integrin αV 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 wa  ...[more]

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