Abstract
High mobility group protein box1 (HMGB1) and its receptor—receptor for advanced glycation end products (RAGE) are pivotal factors in the development and progression of many types of tumor, but the role of HMGB1-RAGE axis in hepatocellular carcinoma (HCC) especially its effects on metastasis and recurrence remains obscure. Here, we report the role of HMGB1-RAGE axis in the biological behaviors of HCC cell lines and the underlying molecular mechanism. We show that the expressions of HMGB1, RAGE, and extracellular HMGB1 increase consistently according to cell metastasis potentials, while the concentration of soluble form of RAGE (sRAGE) is inversely related to metastasis potential of HCC cells. Furthermore, our data show that rhHMGB1 promotes cellular proliferation, migration, and invasion, and increases the level of nuclear factor kappa B (NF-κB), while administrations of HMGB1-siRNA, RAGE-siRNA, anti-HMGB1 neutralizing antibody, anti-RAGE neutralizing antibody, and sRAGE inhibit cellular proliferation, migration, and invasion. Moreover, we also demonstrate that the expression of NF-кB is inhibited by knockdown of HMGB1 or RAGE. Collectively, these data demonstrate that HMGB1 activates RAGE signaling pathways and induces NF-кB activation to promote cellular proliferation, invasion, and metastasis, in HCC cell lines. Taken together, HMGB1-RAGE axis may become a potential target in HCC therapy.
Highlights
Hepatocellular carcinoma (HCC) is one of the most common malignancies around the world, especially in Asia andMol Cell Biochem (2014) 390:271–280Africa
To study the role of High mobility group protein box1 (HMGB1) and receptor for advanced glycation end products (RAGE) in hepatocellular carcinoma (HCC) cells, we first examined the expressions of HMGB1 and RAGE in HCC cells with distinct metastasis potentials by RT-PCR and western blot
These results indicate that the expressions of HMGB1 and RAGE mRNA and proteins are related to the metastasis potentials of HCC cells
Summary
Hepatocellular carcinoma (HCC) is one of the most common malignancies around the world, especially in Asia andMol Cell Biochem (2014) 390:271–280Africa. HMGB1 binds with DNA and serves as a structural component. It can be released into the extracellular environment during necrosis or in response to certain stimulations, such as hypoxia and endotoxin [2]. Through the binding with high affinity to several receptors, extracellular HMGB1 plays a critical role in the development of various diseases, such as vascular disease, diabetes, cancer, and neurodegeneration [3]. Previous study found that HMGB1 and RAGE can modulate the proliferation of HCC cells and induce apoptosis, indicating that HMBG1-RAGE axis may play a significant role in the development of HCC [9, 10]
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