Oncogene-dependent function of BRG1 in hepatocarcinogenesis.
Animals
Carcinogenesis
/ genetics
Carcinoma, Hepatocellular
/ genetics
DNA Helicases
/ genetics
Databases, Genetic
Female
Gene Expression Regulation, Neoplastic
Genes, Tumor Suppressor
Genes, ras
Hepatocytes
/ metabolism
Humans
Liver Neoplasms
/ genetics
Male
Mice, Inbred C57BL
Mice, Knockout
Nuclear Proteins
/ genetics
Oncogenes
Proto-Oncogene Proteins c-met
/ genetics
Transcription Factors
/ genetics
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
04 02 2020
04 02 2020
Historique:
received:
05
09
2019
accepted:
15
11
2019
revised:
14
11
2019
entrez:
6
2
2020
pubmed:
6
2
2020
medline:
10
3
2021
Statut:
epublish
Résumé
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 (NRAS
Identifiants
pubmed: 32019910
doi: 10.1038/s41419-020-2289-3
pii: 10.1038/s41419-020-2289-3
pmc: PMC7000409
doi:
Substances chimiques
Nuclear Proteins
0
Transcription Factors
0
Proto-Oncogene Proteins c-met
EC 2.7.10.1
SMARCA4 protein, human
EC 3.6.1.-
Smarca4 protein, mouse
EC 3.6.1.-
DNA Helicases
EC 3.6.4.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
91Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK026743
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA136606
Pays : United States
Organisme : NCI NIH HHS
ID : R03 CA208215
Pays : United States
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