MicroRNA-143 as a Tumor Suppressor for Bladder Cancer

Purpose

We investigated the expression and involvement of miRNA in bladder cancer.

Materials and Methods

An miRNA array was used to examine the differential expression of miRNA in tumor tissues and normal matched controls. The expression of miRNA-143 was confirmed by Northern blot and real-time polymerase chain reaction. The functional role of miRNA-143 in bladder cancer was studied by examining cell proliferation and oncogene expression after miRNA-143 transfection into 2 transitional carcinoma cell lines.

Results

miRNA profiling of human bladder cancer and matched normal urothelial epithelium controls revealed that 37 miRNAs were up-regulated and 38 were down-regulated in cancer tissues, of which the expression of miRNA-143 was 13.7 times lower in tumor than in the matched control. Consistent with microarray data, Northern blot analysis and real-time polymerase chain reaction confirmed that miRNA-143 expression was significantly down-regulated in bladder tumor tissues compared with normal adjacent tissues. The expression of miRNA-143 was not detected in the 2 human bladder cancer cell lines EJ and T24. Interestingly miRNA-143 transfection into EJ and T24 cells significantly inhibited cell proliferation. RAS protein expression in cancer tissues was much higher than in adjacent controls. Consistently RAS protein expression was also significantly decreased in miRNA-143 transfected cells compared with nonspecific miRNA transfected cells.

Conclusions

miRNAs are differentially expressed in bladder cancer tissues. miRNA-143 may function as a tumor suppressor in bladder transitional cell carcinoma.

Key Words: urinary bladder, carcinoma, transitional cell, microRNAs, microarray analysis

Abbreviations and Acronyms: ERK, extracellular regulated kinase, miRNA, microRNA, PCR, polymerase chain reaction, q, quantitative, RT, real-time, snRNA, small noncoding RNA, UTR, untranslated region