Journal
ONCOTARGET
Volume 7, Issue 29, Pages 45863-45875Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.10244
Keywords
ARID2; SWI/SNF complex; the Rb/E2F pathway; hepatocellular carcinoma; cell-cycle arrest
Categories
Funding
- Major National ST program [2013ZX10002002-005-003]
- China National Natural Science Foundation [81572683, 81371827]
- Natural Science Foundation Project of Chongqing Science & Technology Commission [cstc2015jcyjBX0011, cstc2012jja10135]
- Outstanding Young talent program of Second Affiliated Hospital of Chongqing Medical University
- CQMU [201401]
Ask authors/readers for more resources
Exome and whole-genome sequencing studies have drawn attention to the role of somatic mutations in SWI/SNF chromatin remodeling complexes in the carcinogenesis of hepatocellular carcinoma (HCC). Here, we explored the molecular mechanisms underlying the biological roles of AT-rich interactive domain 2 (ARID2) in the pathogenesis of HCC. We found that ARID2 expression was significantly downregulated in HCC tissues compared with non-tumorous tissues. Restoration of ARID2 expression in hepatoma cells was sufficient to suppress cell proliferation and tumor growth in mice, whereas ARID2 knockdown contributed to the enhancement of cellular proliferation and tumorigenicity. Suppression of ARID2 expression accelerated G1/S transition associated with upregulation of cyclin D1, cyclin E1, CDK4, and phosphorylation of the retinoblastoma protein (Rb). Furthermore, we demonstrated that ARID2 physically interacts with E2F1 and decreases binding of E2F1/RNA Pol II to the promoters of CCND1 and CCNE1. Taken together, these results demonstrate that ARID2 suppresses tumor cell growth through repression of cyclin D1 and cyclin E1 expression, thereby retarding cell cycle progression and cell proliferation in hepatoma cells. These findings highlight the potential role of ARID2 as a tumor growth suppressor in HCC.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available