The Effect Of Abnormal Wnt Signaling Pathway On The Expression Level Of Histone Acetylation In Bladder Cancer

BackgroundBladder cancer is the fourth most common malignant cancer in men and the ninth in women worldwide.Intravesical immunization or chemotherapy and surgical resection are common methods for the treatment of NMIBC and locally advanced bladder cancer.However,these tumors are prone to recurrence and progression,and 25%of patients are eventually diagnosed with muscle invasive bladder cancer.They need to undergo a radical cystectomy.Wnt signaling pathway is closely related to the occurrence of bladder cancer.Acetylation is the main content of epigenetics,and histone acetylation is a common type of epigenetic modification.Bladder cancer is a highly malignant tumor.The clinical characteristics and immune phenotypes of the bladder cancer are quite different,which affects tumor recurrence and metastasis.The occurrence of bladder cancer is closely related to the abnormality of the Wnt signaling pathway.Kastritis et al.found that the abnormality of the Wnt signaling pathway was involved in the occurrence of bladder cancer.Hirata et al.found thatβ-catenin expression was significantly increased in bladder cancer,which was the key protein of the gene.Acetylation is the main content of epigenetics,among them,histone acetylation is a common type of epigenetic modification.Histone acetylation is dynamically regulated by two enzymes,which are generally composed of histone acetyltransferase and histone deacetylase.Histone acetyltransferase and histone deacetylase are coordinated and regulated together.If these two enzymes are imbalanced,it will lead to tumor development.Histone H3,H4 lysine residue N-segment acetylation modification is the main way of histone modification.This experiment focuses on observing the expression of Wntl,β-catenin and H3K9ac in bladder tumor tissue and normal adjacent tissues,and analyzes the correlation between the expression of histone acetylation and Wnt,β-catenin expression,and explores the abnormality of Wnt signaling pathway effect on the level of histone acetylation expression.Abnormal Wnt signaling pathway plays a significant role in the occurrence and development of bladder tumors.To acquaintance the influence on the abnormal Wnt signaling pathway and histone acetylation,and to provide an experimental basis for further research on histone acetylation in bladder cancer.ObjectiveTo observe the expression of Wntl,P-catenin and H3K9ac in bladder tumor tissues and normal adjacent tissues,to analysis the correlation between the expression level of histone acetylation and the expression of Wnt and β-catenin,and to investigate the effect of abnormal Wnt signaling pathway on the expression level of histone acetylation.MethodsThe total specimens of bladder tumors from our hospital were collected,and 32 cases of tumor tissue and normal adjacent tissues were taken,then the expression levels of Wntl,β-catenin and H3K9ac relative protein were detected by Western blot and the expression levels of Wntl,β-catenin and H3K9ac mRNA were detected by RT-qPCR.Statistical analysis of the difference between the tumor tissue and normal adjacent tissue and the correlation between the expression levels of Wnt and β-catenin and histone acetylation.Results1.Western Blot detection of Wntl,β-catenin,H3K9ac relative protein expression in different groups of samples.Western Blot test results showed that Wntl and β-catenin were highly expressed in tumor tissues compared with normal cancer tissues,and the difference was statistical significance(P<0.05).H3K9ac was lowly expressed in tumor tissues,and H3K9ac had a significant statistical difference(P<0.05).2.RT-qPCR was used to detect the expression of Wnt,β-catenin and H3K9ac mRNA in different groups of samples.The results showed that compared with normal cancer tissues,Wntl and β-catenin mRNA were highly expressed in tumor tissues,with statistical significance(P<0.05).H3K9ac mRNA expression was low in tumor tissues,and H3K9ac mRNA had a significant statistical difference(P<0.05).3.Correlation test of Wntl,β-catenin and H3K9ac protein expression in tumor tissues.Pearson correlation coefficients r=0.013 and P=0.943 of two variables of Wntl and H3K9ac,and the correlation coefficient was not statistically significant(P>0.05).The Pearson correlation coefficients of H3K9ac and β-catenin were r 0.123,P=0.501,and the correlation coefficients were not statistically significant(P>0.05).4.Correlation test of Wntl,β-catenin and H3K9ac mRNA expression in tumor tissues.Pearson correlation coefficients were =0.088,P=0.634 of Wntl and H3K9ac,and the correlation coefficients were not statistically significant(P>0.05).The Pearson correlation coefficients of H3K9ac and β-catenin were r=0.172,P=0.348,and the correlation coefficients were not statistically significant(P>0.05).ConclusionWnt and β-catenin were highly expressed in bladder cancer tissues,and H3K9ac was down-regulated.Histone acetylation was not associated with the expression of Wnt and β-catenin,and the decrease of histone acetylation level may be related to the occurrence and development of bladder cancer.The low expression of acetylated histones was involved in the occurrence and development of tumors,but it was not related to the abnormality of the Wnt signaling pathway.The abnormality of the Wnt signaling pathway may affect the occurrence and development of tumors by regulating other epigenetic content.In bladder cancer,however,acetylated histones may be regulated by other signaling pathway molecules.The discovery of new acetylated histone pathways and how to reduce acetylated histones may provide new ideas for the treatment of bladder cancer and the prognosis of patients.