机构：[1]Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA.[2]Department of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.四川大学华西医院[3]Systems Biology Center, NHLBI, NIH, 9000 Rockville Pike, Bethesda, MD 20892, USA.[4]Institute of Pathology, University of Regensburg, Regensburg, Germany.[5]Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University (Air Force Medical University), Xi’an, China.[6]Department of Hepatobiliary Surgery, Xijing Hospital, Air Force Military Medical University, Xi’an, China[7]Department of Medical, Surgical, and Experimental Sciences, University of Sassari, Sassari, Italy
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.
基金：
This work was supported by
NIH grants R03CA208215 and R01CA136606 to X.C., and P30DK026743 for
UCSF Liver Center.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2020]版：
大类|2 区生物学
小类|2 区细胞生物学
最新[2023]版：
大类|1 区生物学
小类|2 区细胞生物学
第一作者：
第一作者机构：[1]Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA.
共同第一作者：
通讯作者：
通讯机构：[4]Institute of Pathology, University of Regensburg, Regensburg, Germany.[7]Department of Medical, Surgical, and Experimental Sciences, University of Sassari, Sassari, Italy
推荐引用方式(GB/T 7714)：
Pan Wang,Xinhua Song,Dan Cao,et al.Oncogene-dependent function of BRG1 in hepatocarcinogenesis.[J].Cell death & disease.2020,11(2):91.doi:10.1038/s41419-020-2289-3.
APA：
Pan Wang,Xinhua Song,Dan Cao,Kairong Cui,Jingxiao Wang...&Xin Chen.(2020).Oncogene-dependent function of BRG1 in hepatocarcinogenesis..Cell death & disease,11,(2)
MLA：
Pan Wang,et al."Oncogene-dependent function of BRG1 in hepatocarcinogenesis.".Cell death & disease 11..2(2020):91
生物学