Molecular and Bioinformatics Analyses Identify 7 Circular RNAs Involved in Regulation of Oncogenic Transformation and Cell Proliferation in Human Bladder Cancer

BACKGROUND Circular RNAs (circRNAs) have emerged as important regulators in carcinogenesis and metastasis. However, the knowledge of circRNAs in bladder cancer remains limited. This study aimed to investigate the role and mechanism of circRNAs in the development and progression of bladder cancer. MATERIAL AND METHODS Three pairs of bladder carcinomas (including high- and low-grade tumors) and adjacent normal tissues were collected from patients. The total RNAs were extracted from these samples and subjected to Clariom D microarray assays to detect the differentially expressed circRNAs and mRNAs. The mRNA targets for these circRNAs were predicted by miRanda in combination with stringent differential mRNA filters. The interaction network for the circRNA-mRNA pairs was generated by Cytoscape. RESULTS Among the 1038 circRNAs detected by the Clariom D microarray assay, we identified 7 significantly differentially expressed circRNAs in the tumors (fold change >2, FDR <0.05). Principal component analysis of the differential circRNAs confirmed that the tumor samples were separated from the normal samples. Hierarchical clustering analyses on these RNAs and their predicted mRNA targets showed that the majority of differentially expressed circRNAs and mRNAs had been up-regulated in the bladder tumors. KEGG signaling pathway analysis has indicated that genes involved in cell proliferation, oncogenic transformation, and metastasis are potentially regulated by these circRNAs. CONCLUSIONS The current study provides a molecular basis for further investigating the mechanisms by which circRNAs regulate bladder cancer. The clinical significance of the identified circRNAs is highlighted by their potentials as diagnostic and prognostic biomarkers for bladder cancer patients.