Identification of a potentially functional circRNA-miRNA-mRNA ceRNA regulatory network in bladder cancer by analysis of microarray data.

Abstract

BackgroundCircular RNAs (circRNAs) have received increasing attention in cancer development. However, a substantial number of circRNAs still require characterization. The purpose of this study is to uncover novel circRNAs and their molecular mechanism in bladder cancer (BCa).MethodsA combinative strategy of extensive data mining and computational biology was employed to identify BCa-related circRNAs and explore their potential mechanisms of action.ResultsThree differentially expressed circRNAs (has_circ_0023642, has_circ_0047322, has_circ_0041151) were obtained from the microarray dataset (GSE92675). Four miRNAs (miR-616, miR-515-5p, miR-647, miR-1178) with potential binding sites with these three circRNAs were identified. Pathway analysis demonstrated that all four miRNAs were closely associated with some cancer-related pathways. Survival analysis indicated that these miRNAs might potentially play a role in tumor-suppressive functions in BCa. Subsequently, 181 overlapping genes were identified from 472 up-regulated genes in BCa (TCGA database), and 10,017 predicted target genes of the four miRNAs obtained. A circRNA-miRNA-mRNA network was constructed on the identified three circRNAs, four miRNAs, and 181 overlapping genes. Besides, six hub genes (CENPA, HIST1H2BJ, HIST1H2BO, HIST1H3H, HIST1H3B, HIST1H3F) were identified from establishing a protein-protein interaction (PPI) network on the same overlapping genes. Furthermore, a circRNA-miRNA-hub gene sub-network was built to delineate the links among the differential circRNAs, miRNA, and hub genes.ConclusionsOur study provided significant insights into the molecular mechanisms that regulate the progression of BCa from the circRNA-miRNA-mRNA network view.