The role of receptor for advanced glycation end products (RAGE) in the proliferation of hepatocellular carcinoma

Al Madhagi Yaser, Yan Huang, Rong Rong Zhou, Guan Sheng Hu, Mei Fang Xiao, Zhe Bing Huang, Chao Jun Duan, Wei Tian, Dao Lin Tang, Xue Gong Fan

Research output: Contribution to journalArticle

35 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)5982-5997
Number of pages16
JournalInternational journal of molecular sciences
Volume13
Issue number5
DOIs
StatePublished - May 1 2012
Externally publishedYes

Keywords

  • HMGB1
  • NF-κb
  • Proliferation
  • RAGE
  • SiRNA

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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  • Cite this

    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. (2012). The role of receptor for advanced glycation end products (RAGE) in the proliferation of hepatocellular carcinoma. International journal of molecular sciences, 13(5), 5982-5997. https://doi.org/10.3390/ijms13055982