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Oncogene-dependent function of BRG1 in hepatocarcinogenesis.

Abstract：

:Hepatocellular carcinoma (HCC) is the major type of primary liver cancer. Genomic studies have revealed that HCC is a heterogeneous disease with multiple subtypes. BRG1, encoded by the SMARCA4 gene, is a key component of SWI/SNF chromatin-remodeling complexes. Based on TCGA studies, somatic mutations of SMARCA4 occur in ~3% of human HCC samples. Additional studies suggest that BRG1 is overexpressed in human HCC specimens and may promote HCC growth and invasion. However, the precise functional roles of BRG1 in HCC remain poorly delineated. Here, we analyzed BRG1 in human HCC samples as well as in mouse models. We found that BRG1 is overexpressed in most of human HCC samples, especially in those associated with poorer prognosis. BRG1 expression levels positively correlate with cell cycle and negatively with metabolic pathways in the Cancer Genome Atlas (TCGA) human HCC data set. In a murine HCC model induced by c-MYC overexpression, ablation of the Brg1 gene completely repressed HCC formation. In striking contrast, however, we discovered that concomitant deletion of Brg1 and overexpression of c-Met or mutant NRas (NRASV12) triggered HCC formation in mice. Altogether, the present data indicate that BRG1 possesses both oncogenic and tumor-suppressing roles depending on the oncogenic stimuli during hepatocarcinogenesis.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Wang P,Song X,Cao D,Cui K,Wang J,Utpatel K,Shang R,Wang H,Che L,Evert M,Zhao K,Calvisi DF,Chen X

doi

10.1038/s41419-020-2289-3

subject

Has Abstract

pub_date

2020-02-04 00:00:00

pages

91

issue

2

issn

2041-4889

pii

10.1038/s41419-020-2289-3

journal_volume

11

pub_type

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