title: The Role of receptor for Advanced Glycation End Products (RAGE) in the proliferation of hepatocellular carcinoma.
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.
authors: Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha 410008, China.
authors: Al-Madhagi
authors: AM
authors: Yaser
authors: Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha 410008, China.
authors: Yan
authors: Y
authors: Huang
authors: Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha 410008, China.
authors: Rong-Rong
authors: RR
authors: Zhou
authors: Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha 410008, China.
authors: Guan-Sheng
authors: GS
authors: Hu
authors: Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha 410008, China.
authors: Mei-Fang
authors: MF
authors: Xiao
authors: Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha 410008, China.
authors: Zhe-Bing
authors: ZB
authors: Huang
authors: Medical Science Institute, Xiangya Hospital, Central South University, Changsha 410008, China.
authors: Chao-Jun
authors: CJ
authors: Duan
authors: Immunogenetics Research Group, Department of Immunology, College of Basic Medical Sciences Central South University, Changsha 410013, China.
authors: Wei
authors: W
authors: Tian
authors: Department of Surgery, Hillman Cancer Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15219, USA.
authors: Dao-Lin
authors: DL
authors: Tang
authors: Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha 410008, China.
authors: Xue-Gong
authors: XG
authors: Fan
mesh_terms: D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D055785:Gene Knockdown Techniques; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D000067759:Receptor for Advanced Glycation End Products / Q000235:genetics*; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D024243:HMGB1 Protein; C585491:HMGB1 protein, human; C498143:RELA protein, human; D000067759:Receptor for Advanced Glycation End Products; D051996:Transcription Factor RelA