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The Role of Receptor for Advanced Glycation End Products (RAGE) in the Proliferation of Hepatocellular Carcinoma
Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha 410008, China
Medical Science Institute, Xiangya Hospital, Central South University, Changsha 410008, China
Immunogenetics Research Group, Department of Immunology, College of Basic Medical Sciences Central South University, Changsha 410013, China
Department of Surgery, Hillman Cancer Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15219, USA
* Author to whom correspondence should be addressed.
Received: 22 March 2012; in revised form: 9 May 2012 / Accepted: 14 May 2012 / Published: 18 May 2012
Abstract: The receptor for advanced glycation end products (RAGE) is oncogenic and overexpressed in human cancers, but its role in hepatocellular carcinoma remains unclear. Here we demonstrated that RAGE is overexpressed in primary hepatocellular carcinoma (PHC) compared to adjacent para-neoplastic liver samples. Serum endogenous secretory RAGE levels were also increased in PHC patients (p < 0.01). Moreover, we demonstrated that RAGE regulates cellular proliferation in Hepatocellular carcinoma (HCC). Knockdown of RAGE by specific siRNA inhibited cellular growth in the hepatocellular carcinoma cell line, Huh7, whereas the RAGE ligand, high mobility group box 1 protein (HMGB1) increased cellular proliferation. In addition, knockdown of RAGE by siRNA arrested cells in the G1 phase and inhibited DNA synthesis (p < 0.01), while HMGB1 protein decreased the number of cells in the G1 phase and increased the number in the S phase (p < 0.05). Furthermore, quantitative real time RT-PCR (qRT-PCR) and Western Blot results demonstrated that RAGE and HMGB1 positively regulate NF-κB p65 expression in Huh7 cells. These studies suggest that RAGE and RAGE ligands are important targets for therapeutic intervention in hepatocellular carcinoma.
Keywords: RAGE; HMGB1; siRNA; NF-κB; proliferation
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Yaser, A.-M.; Huang, Y.; Zhou, R.-R.; Hu, G.-S.; Xiao, M.-F.; Huang, Z.-B.; Duan, C.-J.; Tian, W.; Tang, D.-L.; Fan, X.-G. The Role of Receptor for Advanced Glycation End Products (RAGE) in the Proliferation of Hepatocellular Carcinoma. Int. J. Mol. Sci. 2012, 13, 5982-5997.
Yaser A-M, Huang Y, Zhou R-R, Hu G-S, Xiao M-F, Huang Z-B, Duan C-J, Tian W, Tang D-L, Fan X-G. The Role of Receptor for Advanced Glycation End Products (RAGE) in the Proliferation of Hepatocellular Carcinoma. International Journal of Molecular Sciences. 2012; 13(5):5982-5997.
Yaser, Al-Madhagi; Huang, Yan; Zhou, Rong-Rong; Hu, Guan-Sheng; Xiao, Mei-Fang; Huang, Zhe-Bing; Duan, Chao-Jun; Tian, Wei; Tang, Dao-Lin; Fan, Xue-Gong. 2012. "The Role of Receptor for Advanced Glycation End Products (RAGE) in the Proliferation of Hepatocellular Carcinoma." Int. J. Mol. Sci. 13, no. 5: 5982-5997.