Exploration of bladder cancer molecular mechanisms based on miRNA-mRNA regulatory network.

To explore the complex molecular mechanisms of bladder cancer, mRNA and miRNA expression profiles were combined for systematic analyses. A total of 18 common differentially expressed genes (DEGs) were identified from two mRNA expression datasets which consisted of 206 tumor and 74 normal tissues. Then, survival analysis based on the SurvExpress database showed that the common DEGs were able to significantly differentiate low- and high-risk groups in 4 public bladder cancer datasets (p<0.01). Notably, the tumor and normal samples were able to be almost clearly classified into 4 groups based on these identified common DEGs. In addition, 6 out of the 18 common DEGs, including ALDH1A1 and SRPX, are regulated by 6 reported miRNAs based on regulatory network analyses. Expression levels of the 6 DEGs were validated in 10 bladder cancer samples using RT-PCR, and the expression values were concordant with the microarray results. Collectively, our analyses indicated that various biological processes are involved in the development and progression of bladder cancer. Firstly, cell cycle checkpoints and DNA repair networks of cancer stem-like cells were regulated by high expression of ALDH1A1, and hence promoted tumor self-renewal or metastasis. Then, activation of HspB6 induced the angiogenesis process which provides necessary nutrition and oxygen for tumor cells. Moreover, downregulation of the expression of tumor-suppressor genes SRPX and FLNC further promoted apoptosis and metastasis. The identification of potential biological processes and genes can be helpful for the understanding of bladder cancer molecular mechanisms.