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

International Journal of Molecular Sciences

Al-Madhagi Yaser²  Yan Huang²  Rong-Rong Zhou²  Guan-Sheng Hu²  Mei-Fang Xiao²  Zhe-Bing Huang²  Chao-Jun Duan¹  Wei Tian⁴  Dao-Lin Tang³ 

[1] Medical Science Institute, Xiangya Hospital, Central South University, Changsha 410008, China; E-Mail:;Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha 410008, China; E-Mails:;Department of Surgery, Hillman Cancer Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15219, USA; E-Mail:;Immunogenetics Research Group, Department of Immunology, College of Basic Medical Sciences Central South University, Changsha 410013, China; E-Mail:

关键词: RAGE;    HMGB1;    siRNA;    NF-κB;    proliferation;   

DOI  :  10.3390/ijms13055982

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2012 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.