To Intvestigate The Role Of RBM10 In The Development Of Renal Carcinoma Using Human Tissue Samples And Mouse Uninephrectomy Model

RNA binding motif 10(RBM10)is one of the many members of the RBM family of proteins.RBM10 is not only related to the expression of RNA transcription and translation genes,cell cycle and apoptosis regulation,but also related to multiple cell signal transduction pathways,playing an important role in the occurrence and development of tumors.In recent years,more and more studies have highlighted the clinical importance of RBM10 mutation,which can lead to the up-regulation of RBM10 expression in congenital dysplasia syndrome and a variety of cancers,and is related to advanced clinicopathological parameters.However,the role and mechanism of RBM10 in the pathogenesis of RBM10 need further study.Objective: The uninephrectomy mouse model was established and the renal cell carcinoma model was established by using the uninephrectomy mouse model,and the expression difference of RBM10 in the pathogenesis of renal cell carcinoma was determined.The difference in expression between cancer and non-cancer kidney tissue was verified in clinical tissue samples.To explore the role and possible mechanism of RBM10 in the development and progression of renal cell carcinoma.Methods: 1.The cancer genome atlas(TCGA)data were used to analyze the expression of RBM10 protein in different subtypes of renal cell carcinoma and paracancer non-carcerous renal tissue,as well as the overall survival curve of patients with different RBM10 expression.2.Immunohistochemical analysis of RBM10 expression in human tissue samples of two common types of renal cell carcinoma(papillary renal carcinoma and clear cell carcinoma),and its correlation with clinicopathological characters.3.The renal cell carcinoma model was established by uninephrectomy in mice.The body weight,kidney weight,kidney body weight index of the mice were recorded and analyzed statistically.4.H&E staining was used to detect the immunophenotype of neoplastic renal epithelium and compare it with that of renal tubules to identify its histological origin.Results: 1.By mining TCGA datebase,it was found that RBM10 was up-regulated in two common types of renal cell carcinoma(papillary renal carcinoma and clear renal cell carcinoma)tissues compared with adjacent non-cancerous tissues;High expression of RBM10 is associated with poor clinical prognosis.2.Immunohistochemical analysis of human renal cell carcinoma showed that the expression level of RBM10 in the two types of renal cell carcinoma tissue was higher than that in the non-cancerous kidney tissue(P<0.05);The expression level of RBM10 in renal cell carcinoma was correlated with tumor size(P<0.05),the expression level of RBM10 in clear renal cell carcinoma was correlated with TNM stage(P<0.05),while not correlated with gender,age,distant metastasis and lymph node metastasis(P > 0.05).3.The mouse uninephrectomy kidney resection model was successfully constructed by laparotomy of the left kidney of the mouse.4.H&E staining showed atypical proliferation of proximal renal tubules in uninephrectomy mice,but no significant change in proximal renal tubules in sham operation group.The expression of CAIX,CD10,CD117,CK7,Ki67,RBM10,P504 S PAS-8 and other factors related to renal cell carcinoma were different between atypical tubules with proximal convoluted tubules or distal convoluted tubules in the renal tissue of uninephrectomy mice,and the immunophenotype supported that atypical tubules originated from proximal convoluted tubule.Conclusion: 1.The up-regulated RBM10 in papillary and clear renal cell carcinoma in human tissues and in atypical renal tubules in uninephrectomy mice model suggests that RBM10 has a potential carcinogenic role in the development of renal cell carcinoma.2.The up-regulated of RBM10 expression in clinical tissue specimens was associated with some advanced clinicopathological characters.Meanwhile,TCGA data analysis showed that high expression of RBM10 was associated with decreased overall survival in patients with papillary renal carcinoma and clear renal cell carcinoma,suggesting that RBM10 plays an important role in the progression of renal cellcarcinoma.3.The model of atypical proliferation of renal tubules in C57BL/6J mice was successfully constructed by uninephrectomy.Histological morphology and immunophenotype indicated that atypical tubules originate from proximal convoluted tubules.