Analysis Of The Expression And Biological Function Of SMARCC1 In Bladder Cancer

Background: Bladder cancer(BC)is a common malignant tumor in the urinary system,which was the thirteenth most common cause of cancer death in the world.The incidence of BC is also increasing year by year.At present,diagnosis of BC depends on cystoscopy pathological biopsy.The treatment of early limited BC is mainly surgical treatment,but bladder cancer has the high risk of recurrence and progression.Therefore,we further understand the molecular biological mechanism of occurrence and development of BC by exploring the abnormal expression,clinical significance and biological function of SMARCC1 gene in BC.Methods: The expression of SMARCC1 in 30 cases of BC and its adjacent tissues was detected by RT-q PCR.Immunohistochemical method was used to analyze the relationship between the expression of SMARCC1 and age,sex,TNM and other clinicopathological features and prognosis in 54 cases of bladder cancer.Western Blot method was used to detect the expression of SMARCC1 in human normal bladder urothelial cells(SV-HUC-1)and 6 BC cell lines(SW780,5637,T24,UMUC-3,TCCSUP,J82),moreover,2 cell lines(SW780 和 UMUC-3)with high expression specificity were screened.In order to explore the biological role of SMARCC1 in the occurrence and development of BC,we specifically knocked down the expression of SMARCC1 in these two cell lines(SW780 和 UMUC-3).The effects of SMARCC1 on the proliferation of bladder cancer cells were detected by CCK-8 kit,and the changes of cell cycle and apoptosis were analyzed by flow cytometry.The migration abilities of cells were detected by Transwell test.After knocking down the expression of KPNA2,NUP153 and NUP50 in tumor cells,the expression of SMARCC1 in cytoplasm and nucleus of bladder cancer were detected by WB.The protein interaction between SMARCC1 and KPNA2 were examined by protein CO-IP.Finally,the tumor model of nude mice were established to detect the effect of knocking down the expression of SMARCC1 on the tumor growth of BC cells in vivo.Results: The RT-q PCR results of 30 clinical BC patients and matched adjacent tissues showed that the expression of SMARCC1 in 30 tumor samples was significantly higher than that in paired paracancerous samples.The results of immunohistochemical staining in 54 cases of bladder cancer showed that high expression of SMARCC1 was positively correlated with T stage and resulted in poor prognosis.RT-qPCR and Western Blot showed that the expression of SMARCC1 in BC cell lines SW780 and UMUC-3 were significantly higher than that in normal human bladder epithelial cells SV-HUC-1.Compared with the control group,CCK-8assay showed that down-regulation of SMACC1 expression could inhibit tumor cell proliferation.Flow cytometry showed that knockdown of SMARCC1 expression induced tumor cell apoptosis and G1/S cell cycle arrest.Transwell assay showed that low expression of SMARCC1 inhibited the migration of BLCA cells.After down-regulating the expression of nuclear transport-related proteins KPNA2,NUP153 and NUP50 in BC cell lines,the nuclear translocation of SMARCC1 were inhibits.CO-IP confirmed the interaction between SMARCC1 and KPNA2.The results of tumorigenesis in nude mice showed that the volume and weight of tumors in the experimental group were significantly lower than those in the control group after subcutaneous inoculation of tumor cells for 24 days.Conclusions: The expression of SMARCC1 were significantly increased in BC tissues and cell lines and the high expression of SMARCC1 were positively correlated with T stage of BC and showed poor prognosis.Knockdown the expression of SMARCC1 could significantly inhibit the proliferation and migration and induce apoptosis and G1 / S phase arrest of tumor cells.KPNA2 could interact with SMARCC1 and mediate its physiological function.Down-regulate the expression of SMARCC1 reduced the risk of tumorigenesis in vivo.