The Role And Mechanism Of Epigenetic Factor KMT2D In The Development And Development Of Bladder Cancer

Objective: To explore the role of epigenetic factor KMT2 D in the development and progression of bladder cancer and its possible mechanism.Methods: 1.The mutation,expression and prognosis of KMT2 family members in patients with bladder cancer were analyzed by consulting public databases,and the expression of KMT2 D protein was verified by collected specimens of patients with bladder cancer.2.Screening of bladder cancer cell lines with high expression KMT2 D gene by consulting public databases and verifying by immunofluorescence staining.3.KMT2 D gene knockdown stable transfer strain was constructed by lentiviral vector and verified by western blotting experiment and RT-q PCR experiment.4.The changes in the proliferation capacity of bladder cancer cells after knocking out KMT2 D gene were detected by MTT experiment and organoid culture experiment.5.The migration ability of bladder cancer cells after knocking out KMT2 D gene was detected by cell scratch experiment and Transwell migration experiment.6.Bioinformatics analysis,transcriptome sequencing,western blotting experiment and RT-q PCR experiment were used to explore the potential molecular mechanism of KMT2 D gene knockdown on the biological function of bladder cancer cells.7.Statistical analysis software was used to conduct statistical analysis on the obtained experimental data.When the P value was less than 0.05,the difference between the two groups was considered to be statistically significant.Results: 1.By consulting the c Bio Portal database,it was found that KMT2 D gene showed high mutation frequency in bladder cancer,and the mutation type was mostly loss-of-function mutation,which led to a general decline in KMT2 D gene expression in bladder cancer patients.The use of surgical specimens from hospital bladder cancer patients showed that the expression of KMT2 D protein in cancer tissues was significantly lower than that in adjacent tissues.2.Bladder cancer cell line SW780 and T24 cells have high expression of KMT2 D gene,which can be used to construct KMT2 D gene knockdown line.3.After knocking down the KMT2 D gene expression of bladder cancer cell SW780,its cell proliferation ability increased significantly.4.After knocking down the KMT2 D gene expression of bladder cancer cell line T24,its cell migration ability increased significantly.5.Knocking down KMT2 D gene significantly upregulates TP63 gene expression.Specifically,the expression of ΔNp63 protein in SW780 cells of bladder cancer increased significantly after knocking out the KMT2 D gene.However,the expression of TAp63 protein decreased significantly in bladder cancer T24 cells after knocking down KMT2 D gene.Conclusion(s): The KMT2 D gene is a cancer suppressor for bladder cancer.Knocking down KMT2 D gene expression in bladder cancer cell lines can promote cell proliferation or migration,and its mechanism of action may be by maintaining TAp63 protein expression in bladder cancer cells or inhibiting ΔNp63 protein expression.