Nucleoporin 210 Serves a Key Scaffold for SMARCB1 in Liver Cancer

Abstract The roles of chromatin remodelers and their underlying mechanisms action in cancer remain unclear. In this study, SMARCB1, known initially as a bona fide tumor suppressor gene, was investigated liver cancer. SMARCB1 highly upregulated patients with associated poor prognosis. Loss- gain-of-function studies cells revealed that loss led to reduced cell proliferation, wound healing capacity, growth vivo. Although appeared contribute switch/sucrose nonfermentable (SWI/SNF) complex stability integrity, it did not act using its pathways antagonism EZH2 or association between TP53 AMPK. knockdown induced mild reduction global H3K27 acetylation, immunoprecipitation sequencing acetylated histone antibodies before after identified Nucleoporin210 (NUP210) critical target which bound enhancer changed H3K27Ac enrichment downstream gene expression, particularly cholesterol homeostasis xenobiotic metabolism. Notably, NUP210 only putative supporter involved but also acted key scaffold for P300 chromatin. Furthermore, deficiency conferred sensitivity doxorubicin inhibitor cells. These findings provide insights into dysregulation show novel associations nucleoporins Significance: This study reveals protumorigenic role describes valuable links by identifying coregulator remodeling activity.