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SIN3B promotes integrin αV subunit gene transcription and cell migration of hepatocellular carcinoma
Author(s) -
Qianqian Cai,
Yuanyuan Liu,
Ping Zhu,
Chunlang Kang,
Heyang Xu,
Bing Qi,
Rong Wang,
Yiwei Dong,
Xingzhong Wu
Publication year - 2018
Publication title -
journal of molecular cell biology/journal of molecular cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.825
H-Index - 62
eISSN - 1674-2788
pISSN - 1759-4685
DOI - 10.1093/jmcb/mjy050
Subject(s) - integrin , microbiology and biotechnology , integrin, beta 6 , protein subunit , promoter , cd18 , gene expression , chromatin immunoprecipitation , transcription (linguistics) , transcription factor , biology , transcriptional regulation , chemistry , gene , cell , biochemistry , linguistics , philosophy
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 was silenced. Interestingly, SIN3B stimulated integrin αV 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 αV 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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