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The Mechanism Of SOX7 Inhibiting Wnt/?-catenin Signaling Pathway And EMT Process In Bladder Cancer

Posted on:2021-05-18Degree:MasterType:Thesis
Country:ChinaCandidate:Y WuFull Text:PDF
GTID:2404330611458484Subject:Surgery
Abstract/Summary:PDF Full Text Request
ObjectiveAs one of the most common malignant tumors of urinary system,bladder cancer has been in the top ten of new tumors in the world.Bladder cancer has always been the most common malignant tumor of male genitourinary system in China,and its morbidity and mortality are gradually increasing.Among the new cases of bladder cancer,about 75% of the patients are non-muscular invasive bladder cancer(NMIBC),which is mainly treated by bladder preservation,with a high recurrence rate,while about 25% of patients with muscular invasive bladder cancer(MIBC),mostly use multiple methods of comprehensive treatment,but the prognosis is poor.Therefore,the screening of new bladder tumor biomarkers is of great significance for the prevention,diagnosis and treatment of bladder cancer in order to further clarify the molecular mechanism of the occurrence and development of bladder cancer.As an important member of the SOX family,SOX7 participates in many embryonic development processes.At present,more and more studies have proved that SOX7 plays an important role in the occurrence and development of a variety of tumors,participating in tumor immunity,angiogenesis,migration and invasion,and more as a tumor suppressor gene.According to the current research,it is reasonable to explain that SOX7 plays an important role in the occurrence and development of malignant tumors,but there are few reports at home and abroad whether SOX7 plays a role in the occurrence and development of bladder cancer.The purpose of this study is to explore the expression of SOX7 in bladder cancer,to study the role of SOX7 in the proliferation,migration and invasion of bladder cancer,and the potential molecular mechanism of epithelialmesenchymal transformation of bladder cancer cells.MethodsThe expression of SOX7 in bladder cancer tissues,paracancerous tissues,bladder cancer cell lines and immortal urothelial cells of the control group was detected by realtime reverse transcriptase polymerase chain reaction(q RT-PCR)and Western blotting assay.The expression of SOX7 in bladder cancer tissues was detected by immunohistochemistry,and the clinical case materials of bladder cancer tissue microarray were analyzed.To analyze the expression of SOX7 in bladder cancer and the prognosis of bladder cancer.Bladder cancer cell lines were infected with lentivirus overexpressing SOX7,and the stable transformants were screened with puromycin.The expression of SOX7 in T24 cells was higher than that in the control group.In addition,the expression of SOX7 in T24 cells was down-regulated by transient transfection of siRNA,.The effects of overexpression of SOX7 and knockdown of SOX7 on the proliferation of bladder cancer cells were detected by CCK-8 test and plate clone formation assay.The effects of overexpression of SOX7 and knockdown of SOX7 on the migration and invasion of bladder cancer cells were detected by cell scratch test and Transwell chamber test.In addition,bladder cancer cells overexpressing SOX7 were inoculated into nude mice,and the growth of the cells was observed.The effect of overexpression of SOX7 and knockdown of SOX7 on Epithelial-mesenchymal transition(EMT)was detected by Western Blot test,and the effect of overexpression of SOX7 and knockdown of SOX7 on Wnt pathway was detected by Western Blot.ResultsThrough q RT-PCR,Western Blot,immunohistochemistry,the expression of SOX7 in bladder cancer was significantly lower than that in adjacent normal tissues.At the same time,the expression of SOX7 in bladder cancer cell line(UMUC3,5637,T24,J82)was significantly lower than that in normal urothelial cell line(SV-HUC-1).SOX7 is related to the prognosis of bladder cancer.The prognosis of high expression SOX7 group is better than that of low expression group,especially it is closely related to T stage,grade and tumor size of bladder cancer.After overexpression of SOX7,the proliferation,migration and invasion ability of bladder cancer cells decreased,and the expression of EMT marker protein E-cadherin was significantly increased,while the expression of Ncadherin protein and Vimentin protein was down-regulated.After knocking down SOX7,we can find the opposite result,that is,cell proliferation,migration,invasion ability increased,the expression of E-cadherin protein decreased,while the expression of N-cadherin protein and Vimentin protein increased.In the tumor formation experiment of nude mice,it was found that after overexpression of SOX7,the tumor volume decreased significantly compared with the control group.Through Western Blot experiment,it was found that the expression of SOX7 in bladder cancer was negatively correlated with ?-catenin.ConclusionSOX7 is down-expressed in bladder cancer.As a tumor suppressor gene,it inhibits the progression of EMT in the occurrence and development of bladder cancer,and inhibits the progression of EMT in bladder cancer through wnt/ ?-catenin signal pathway.SOX7 may be a potential biological marker of bladder cancer,plays an important role in the occurrence and development of bladder cancer,and is a potential target for prevention,diagnosis and treatment of bladder cancer.
Keywords/Search Tags:SOX7, bladder cancer, EMT, wnt/?-catenin
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