Expression And Significance Of MicroRNA-200c,ZEB1and ZEB2in Bladder Cancer

Objective:To observe the expression of microRNA-200c, ZEB1and ZEB2(SIP1) in bladder cancer tissue, and to investigate the potential correlation of their expression with clinicopathological features such as number of tumor, tumor size, pathological grade and clinical stage of bladder cancer respectively. To investigate the relationship between the expression of microRNA-200c, ZEB1and ZEB2in bladder cancer in order to provide clues for further studying the role of microRNA-200c in the EMT progress of bladder cancer and its possible molecular mechanism, and to clarify the clinical prognostic significance of them in bladder cancer patients.Methods:We measured the expression level of microRNA-200c in58cases of bladder cancer tissue samples (experimental group) and58normal bladder tissue samples (control group) using quantitative real-time PCR assays. Immunohistochemical staining was performed on the same paraffin-embedded samples to detect the expression of ZEB1and ZEB2. Then we compared the differences of their expression between the two groups by statistical analysis and analyzed the association of their expression with clinicopathological features of bladder cancer and the relevance among their expression.Results:1. The expression levels of microRNA-200c, ZEB1and ZEB2were significantly up-regulated in bladder cancer tissue samples compared with controls (P<0.05).2. The difference of microRNA-200c expression in bladder cancer tissue with number and size was not statistically significant (P>0.05), but the difference with pathological grade and clinical stage was statistically significant. The expression intensity of microRNA-200c was higher in non-muscle invasive bladder cancer than in muscle invasive bladder cancer (P<0.05) and in low-grade bladder cancer than in high-grade bladder cancer (P<0.05).3. The difference of ZEB1and ZEB2expression in bladder cancer tissue with number and size was not statistically significant (P>0.05), but the difference with pathological grade and clinical stage was statistically significant. The immunoreactivity of ZEB1and ZEB2was more frequently detected in muscle invasive bladder cancer than in non-muscle invasive bladder cancer (P<0.05) and in high-grade bladder cancer than in low-grade bladder cancer (P<0.05).4. There was a strong correlation between the expression level of microRNA-200c and the expression of ZEB1in bladder cancer. The expression level of microRNA-200c was significantly higher in ZEB1-negative than in ZEB1-positive samples (P<0.05), but was not significantly different between ZEB2-negative and ZEB2-positive samples (P>0.05).Conclusions:1. The expression levels of microRNA-200c, ZEB1and ZEB2were related to the pathological grade and clinical stage of bladder cancer respectively, which suggests that they may be involved in the genesis and progression of bladder cancer and play important roles in the process of invasion and metastasis. The expression of microRNA-200c, ZEB1and ZEB2detected in bladder cancer contributes to the diagnosis and treatment of bladder cancer, and may be important indicators judging prognosis.2. The strong correlation found between microRNA-200c and ZEB1indicates that the expression of ZEB1may be regulated by microRNA-200c and that ZEB1may be the target of microRNA-200c. Both of them may participate in the progress of EMT in bladder cancer.3. Our study may provide a new research direction to control the invasion and metastasis of bladder cancer. ZEB1and ZEB2may become new intervention targets for the treatment of bladder cancer. MicroRNA-200c could be considered as a novel tumor marker for bladder cancer.