Biological Role And Mechanism Of SOX17 Negatively Regulating YAP In Inhibiting The Progression Of Clear Cell Renal Cell Carcinoma

Objective This study will elucidate the clinical significance of SOX17(sex-determining region Y(SRY)-box transcription factor 17)in ccRCC(clear cell renal cell carcinoma);After increasing or decreasing the expression of SOX17 in 786-O and 769-P,the biological role of SOX17 in ccRCC progression was investigated in vivo and in vitro;To explore the regulatory effect of SOX17 on ccRCC by regulating YAP.Methods Immunohistochemical analysis was performed on the postoperative specimens of patients with ccRCC.Combined with clinicopathological data and follow-up information,the clinical significance and prognostic significance of SOX17 in ccRCC were elucidated through clinical analysis and survival analysis.The renal cell carcinoma cell lines(786-O and 769-P)with stable overexpression of SOX17 and elimination of SOX17 were constructed based on lentivirus transfection and CRISPR/Cas9 system,respectively.The effects of SOX17 on tumor biological characteristics of ccRCC were investigated through proliferation,invasion,migration,apoptosis,subcutaneous tumor formation and drug resistance.The differential signaling pathways between the the control group and the experimental group,SOX17 renal cell lines were knocked out,were screened out by bioinformatics analysis.The expression of YAP continued to be interfered with in renal cell lines with stable knockout of SOX17,so as to determine whether the knockdown of YAP could reduce the regulatory effect of knockdown of SOX17 on ccRCC progression.Results The expression of SOX17 in the tumor tissues of patients with ccRCC was down-regulated,indicating that the postoperative prognosis of patients with ccRCC was poor.The knockout of SOX17 gene can promote the malignant progress of ccRCC and inhibit the sensitivity to targeted drugcs,while the overexpression of SOX17 gene can inhibit the progress of ccRCC and target drug resistance.SOX17 inhibits the malignant progression of ccRCC by negatively regulating YAP.Conclusion SOX17 can be used as a prognostic indicator and tumor suppressor for ccRCC,and it can inhibit the malignant progression of ccRCC by negatively regulating YAP.