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Int. J. Mol. Sci. 2012, 13(5), 5982-5997; doi:10.3390/ijms13055982
Article

The Role of Receptor for Advanced Glycation End Products (RAGE) in the Proliferation of Hepatocellular Carcinoma

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Received: 22 March 2012 / Revised: 9 May 2012 / Accepted: 14 May 2012 / Published: 18 May 2012
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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 RAGE; HMGB1; siRNA; NF-κB; proliferation
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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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.

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