Integrative Networks by BRWD3 Regulates Cytoskeleton Organization and Cell Motility

Abstract

BackgroundEukaryotic cytoskeleton forms and keeps cell shape, transports intracellular particles and organelles, determines cell motility and other important cellular events. A large number of regulators of cytoskeleton organization have been identified, but the detailed regulatory mechanism still remains obscure. Previous reports suggest that BRWD3 may be a regulator of cytoskeleton organization in Drosophila melanogaster, and influences cell shape. Therefore, we investigated the molecular network of BRWD3 regulating cytoskeleton organization.ResultsIn this study, we observed the alteration of cell shape, cell motility, and proliferation when BRWD3 was knocked down in MCF-7 and MDA-MB-231 cell lines. The cells were rounded, cell motility decreased when BRWD3 was knocked down. Using chromatin immunoprecipitation combining with sequencing, we found that BRWD3 influenced the cytoskeleton organization, cell shape, and cell motility through regulating expression of the cytoskeleton associative genes including ARF1, ABI2, ARPC3, ARPC1A, RHOC, MEF2C, and VIM.ConclusionsA molecular network by BRWD3 is sketched to elucidate that BRWD3 may not only regulate actin filament but also regulate microtubule and intermediate filament-based cytoskeleton organization. These efforts provide an overview of a BRWD3 network regulating cytoskeleton organization, cell shape and motility, and allow a better understanding of cytoskeleton (re)organization and pathogenesis of mental retardation X-linked 93 and relative carcinomas.