The Regulatory Role Of SNF5,a Core Subunit OfSWI/SNF Chromatin Remodelingcomplex,in Cellular Proliferation Of Multiplemyeloma

Objective:We sought to determine the effect of SNF5expression on the proliferation of multiple myeloma cells and investigate the mechanism by which SNF5regulates myeloma cell proliferation.Methods:We generated multiple stable cell lines which inducibly express SNF5shRNA in the tetracycline-inducible system. When SNF5was inducibly knocked down, growth curve, flow cytometry and transwell assay were performed to analyze the myeloma cell proliferation or migration. Affymetrix microarray was used to identify the differential expressed genes that are responsible for the growth inhibition conferred by SNF5knockdown. Furthermore, RT-PCR and Western Blot were performed to confirm the expression of several SNF5targets including c-Myc, Cyclin D1, annexin A2, CamKâ…¡ N1å’ŒCamKII D. Finally, we wanted to know whether overexpression of exogenous annexin A2could attenuate the inhibited cell proliferation resulting from SNF5deficiency.Results:Upon SNF5knockdown, the myeloma cell proliferation was markedly suppressed and featured G1arrest, and cell migration was also greatly enhanced. Gene expression profiling suggested that a plethora of genes were potentially regulated by SNF5, which is an essential epigenetic regulator. The decreased expression of several SNF5targets including Cyclin D1, c-Myc, and annexin A2may contribute to the growth inhibition induced by SNF5knockdown.Conclusions:SNF5is required for cellular proliferation of multiple myeloma, and its regulatory function is mediated by its downstream targets such as Cyclin D1, c-Myc, and annexin A2. Thus, our study reveals a novel link between chromatin remodeling and pathogenesis of multiple myeloma.