A Study On The Effect Of BRG1 On Colon Cancer Cell Senescence And Its Potential Mechanism

Cell senescence is one of the key mechanisms involved in tumorgenesis. BRG1 is the specific ATPase of the SWI/SNF chromatin remodeling complex, expressed aberrantly in kinds of tumors. However, it is short of systematic reports about BRGl's effect and its corresponding mechanism in cell senescence. This study shows that BRG1 knockdown promotes colon cancer cell senescence and inhibits proliferation by interfering SIRT1/p53/p21 signal axis. In particular, BRG1 is over expressed in primary tumor and decreased in cell senescence model; BRG1 is inversely correlated with p21 expression; BRG1 knockdown leads to cell vacuolization, up-regulates SA-?-Gal activity, inhibits cell proliferation, induces cell cycle arrest and promotes SAHF formation. In mechanism, BRG1 interferes SIRT's effect on deacetylation of p53 at K382 by binding it, then by which regulates p53/p21 signal pathway to promote senescence and inhibit proliferation. Our study indicates that BRG1/SIRT1/p53 signal axis is a novel mechanism regulating cell senescence and proliferation in colon cancer. Together with the studies of our group, it is showed that BRG1 plays a complicated pro-proliferation and anti-metastasis role in colon cancer tumorgenesis.