GSE159164
RNA-seq in shControl Huh7 and shARID1A Huh7 cells without or with rapamycin treatment
mTORC1 is a conserved central controller of cell growth, which is commonly activated in hepatocellular carcinoma (HCC), driving liver tumorigenesis. In addition to its established cytoplasmic functions, mTORC1 is found in the nucleus where it regulates transcription by all three major RNA polymerases. However, precisely how mTORC1 controls gene expression remains poorly understood. Herein we show that mTORC1 interacts with the BAF SWI/SNF complex and regulates genome-wide chromatin remodeling through ARID1A. Mechanically, mTORC1 stimulates ubiquitination and proteasomal degradation of ARID1A protein through SCF ubiquitin ligase. mTORC1-ARID1A axis promotes chromatin remodeling and expression of YAP target genes, thereby enhancing oncogenic growth in vitro and in vivo. These findings reveal a novel nuclear mTORC1 function and the underlying mechanism that controls oncogenic chromatin remodeling to promote hepatocarcinogenesis. Overall design: shControl Huh7 and shARID1A Huh7 cells without or with 100nM rapamycin treatment for 6 hours