Chromatin remodeling gene ARID2 targets cyclin D1 and cyclin E1 to suppress hepatoma cell progression
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Yujie Duan1,*, Ling Tian1,*, Qingzhu Gao1,*, Li Liang1, Wenlu Zhang1, Yi Yang1, Yaqiu Zheng1, E Pan1, Shengwei Li1, Ni Tang1
1Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, PR China
*These authors contributed equally to this work
Shengwei Li, email: firstname.lastname@example.org
Ni Tang, email: email@example.com
Keywords: ARID2, SWI/SNF complex, the Rb/E2F pathway, hepatocellular carcinoma, cell-cycle arrest
Received: March 02, 2016 Accepted: June 03, 2016 Published: June 23, 2016
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.
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