Receptor for advanced glycation end products (RAGE) partially mediates HMGB1-ERKs activation in clear cell renal cell carcinoma.

Objective: To explore the expression of receptor for advanced glycation end products (RAGE) and high-mobility group box-1 (HMGB1) and their role in clear cell renal cell carcinoma (CCRCC) development and progression.

Methods: Expression of RAGE and HMGB1 was examined in RCC using tissue microarrays. In vitro, quiescent or RAGE-reduced RCC cells were subjected to treatment with HMGB1 and harvested for detecting ERK1/2 phosphorylation via Western blot. Further cell proliferation, migration and invasion were evaluated by Ki-67 immunostaining, wound healing and matrigel invasion assay, respectively.

Results: ①Elevated co-expression of RAGE and HMGB1 in CCRCC was correlated positively with patients' clinical parameters including tumor size, nuclear Fuhrman grade and clinical stage. ②HMGB1 incubation induced ERK1/2 activation in a time- and dose-dependent manner, which could be completely blocked by U0126 (MEK1/2 inhibitor) and partially reversed by RAGE knockdown. ③RAGE knockdown partially reversed the promoted effect of cell proliferation, migration and invasion induced by HMGB1.

Conclusions: HMGB1 promotes the development and progression of CCRCC via ERK1/2 activation, which is partially mediated by RAGE.