Liguo Lin1, Kaihua Zhong, Zhongkai Sun, Guozhong Wu, Guodong Ding. 1. Department of Urinary Surgery, MeiZhou People's Hospital, Meizhou Affiliated Hospital of Sun Yat-sen University, Huangtang Road, Meijiang District, Meizhou, Guangdong Province, 514031, People's Republic of China. linliguo03127@126.com
Abstract
PURPOSE: 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. CONCLUSION: HMGB1 promotes the development and progression of CCRCC via ERK1/2 activation, which is partially mediated by RAGE.
PURPOSE: 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. CONCLUSION:HMGB1 promotes the development and progression of CCRCC via ERK1/2 activation, which is partially mediated by RAGE.
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