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.
Highlights
Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world, especially in Asia and Africa [1]
To determine whether receptors for advanced glycation end products (RAGE) is overexpressed in primary hepatocellular carcinoma, all tissue samples were ground and the cellular extracts or protein lysates were prepared and subjected to quantitative real time PCR and Western Blot analysis
There was no significant difference in the level of RAGE expression between males and females
Summary
Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world, especially in Asia and Africa [1]. RAGE ligands fall into several distinct families They include the High Mobility Group family proteins (including the HMGB1); members of the S100 protein family, and some advanced glycation end products such as carboxymethyllysine (CMLAGE) [9,10,11,12]. HMGB1 is a member of the non-histone, chromatin-associated high mobility group family of proteins [13]. It is widely expressed in many tumor cells and can be secreted by them or be released upon necrotic cell death [14,15]. We used RAGE siRNA and HMGB1 to explore the role of RAGE on the expression of the transcriptional factor NF-κB p65
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