An Experimental Study On The Effects Of HMGB1 Combined With RAGE On The Development Of Renal Cell Carcinoma By Regulating Autophagy

Part ? Clinical study of the expression of HMGB1/RAGE and autophagy in renal cell carcinomaHigh mobility group box 1 protein(HMGB1)is a kind of non-histone protein in chromatin that plays a key role in tumor proliferation,metastasis and immune escape.The receptor for advanced glycation end product(RAGE)is the signal transduction receptor which senses a variety of signalling molecules and has been implicated in a variety of human disease processes including tumorigenisis.Previous studies have demonstrated that HMGB1/RAGE regulated autophagy in different kind of carcinomas.However,the functional role of HMGB1/RAGE in the regulation of Clear cell renal cell carcinoma(cc RCC)autophagy has remained unknown.In the present study,we demonstrate that HMGB1/RAGE and autophagic protein LC3,Beclin-1,PIK3 in clear cell RCC samples was much higher than the adjacent normal tissue by Western blot analysis,q RT-PCR and immunofluorescence.Our results implicated that HMGB1/RAGE and autophagy played an important role in cc RCC and indicated that HMGB1/RAGE might serve as a therapeutictarget for future cc RCC therapy.Part ? The effect of HMGB1/RAGE on the autophagy,apoptosis,migration,proliferation and angiogenesis of renal cell carcinoma cells in vitroHMGB1(high mobility group box 1 protein)is a kind of non-histone protein in chromatin that plays a key role in tumor proliferation,metastasis and immune escape.HMGB1-RAGE interactions have been found to be important in a number of cancers.In the present study,we demonstrated that HMGB1 regulated the cell proliferation,apoptosis and metastasis of the renal cell carcinoma(RCC)cells.Further,we discovered that HMGB1 played an important part in the regulation of autophagic protein LC3 and Beclin-1.Finally,we used a co-culture model of HUVEC and RCC cell line to find out that HMGB1 also had an effect on the expression of VEGF and VEGFR2 in HUVEC.Our results illustrated that HMGB1 mediate RCC cell viability,apoptosis,metastasis,autophagy and angiogenesis,which provided a novel theoretical basis for preventing RCC using HMGB1 as the target.