TY - JOUR T1 - Epigenetic mechanisms underlying OSTβ repression in colorectal cancer JF - Molecular Pharmacology JO - Mol Pharmacol DO - 10.1124/mol.119.118216 SP - mol.119.118216 AU - Ying Zhou AU - Chaonan Ye AU - Yan Lou AU - Junqing Liu AU - Sheng Ye AU - Lu Chen AU - Jinxiu Lei AU - Suhang Guo AU - Su Zeng AU - Yu Lushan Y1 - 2020/01/01 UR - http://molpharm.aspetjournals.org/content/early/2020/01/31/mol.119.118216.abstract N2 - Colorectal cancer (CRC) is the third most common cancer and the fourth-leading cause of cancer-related deaths worldwide. Bile acid, especially deoxycholic acid (DCA) and lithocholic acid (LCA) were reported to play important roles during carcinogenesis of colorectal cancer. In this study, we found OSTβ (Organic solute transporter β), an important bile acid export transporter, was significantly down-regulated in CRC. The repression of OSTβ was identified using Western blot and RT-qPCR. The histone acetylation state at the OSTβ promoter region in vivo and in vitro was evaluated by chromatin immunoprecipitation (ChIP) and trichostation A (TSA) treatment was performed in CRC cell lines HT29 and HCT15. RT-qPCR, siRNA knock-down, ChIP, dual-luciferase reporter gene assay were carried out to find which histone acetyltransferases (HATs) and deacetylases (HDACs) were participated in regulation. We demonstrated that after TSA treatment, OSTβ expression incresed noticeably due to up-regulated H3K27Ac state at OSTβ promoter region. Stimulating the expression of p300 with CTB (an activator of p300), and inhibiting p300 expression with C646 (an inhibitor of p300), si-RNA for p300 could control OSTβ expression through modulating H3K27Ac state at OSTβ promoter region. So, it can be concluded that down-regulated expression of p300 caused low expression of OSTβ in CRC. In general, we revealed epigenetic mechanisms underlying OSTβ repression in CRC, hoping this mechanism would help us to understand carcinogenesis and development of CRC.SIGNIFICANCE STATEMENT OSTβ expression is lower in CRC compared with normal tissues. We demonstrated the epigenetic mechanisms of it and proved that p300 control OSTβ expression through modulating H3K27Ac state at OSTβ promoter region and hence caused low expression of OSTβ in CRC. ER -