TET Methylcytosine Dioxygenase 2 Suppresses Renal Cell Cancer Proliferation And Metastasis By Regulating The MiR-200c-SCD1 Axis

Renal cell carcinoma(RCC)account for more than 80%of adult renal malignant tumor.Because RCC often presents late and has few symptoms and the prognosis is poor,there is an urgent need to seek molecular targets for the diagnosis and treatment of RCC.Previous studies have shown that methylcytosine dioxygenase 2(TET2)can regulate the expression of miR-200c,and miR-200c is an important tumor suppressor in many cancers,such as renal cell carcinoma,lung cancer,gastric cancer,endometrial carcinoma and so on.It is not clear whether miR-200c is regulated by TET2 in renal cell carcinoma.This paper takes renal cell carcinoma as the research object,starting from clinical samples,combined with in vitro and in vivo experiments,to clarify the role of miR-200c in the occurrence and development of renal cell carcinoma and its upstream and downstream regulatory molecular mechanisms,so as to provide scientific basis for finding new drug targets for RCC.In this study,it was found that the expression of TET2 and miR-200c in renal cell carcinoma was significantly lower than that in adjacent normal tissues,and the expression in renal cancer cell line was significantly lower than that in normal renal epithelial cells.There was a positive correlation between the expression of TET2 and miR-200c in renal cell carcinoma.The low expression of TET2 can reduce the methylation level of miR-200c promoter region and promote the expression of miR200c in RCC cells.On the contrary,the high expression of TET2 can increase the methylation level of miR-200c promoter region and inhibit the expression of miR-200c in RCC cells.Knocking down TET2 and miR-200c can inhibit RCC cell proliferation,cell cycle progression,apoptosis and migration,and promote apoptosis,while overexpression of TET2 and miR-200c can promote RCC cell proliferation,cell cycle progression,apoptosis and migration,and inhibit apoptosis.Further exploration found that miR-200c regulates the expression of SCD1 and inhibits the function of RCC cells by targeting.In addition,by building a nude mouse model of renal cell carcinoma,we further proved that TET2 promotes the expression of miR-200c through demethylation,while miR-200c targets to inhibit the expression of SCD1,thus inhibiting the occurrence and development of renal cell carcinoma.In this paper,it is proved that TET2/miR-200c/SCD1 regulatory axis exists in renal cell carcinoma from three aspects:clinical samples,cell level and animal model.TET2,miR-200c and SCD1 may be potential molecular targets for diagnosis and treatment of RCC.