Abstract
BackgroundCircular RNAs (circRNAs) have been shown to interact with microRNAs (miRNA) as competitive endogenous RNAs (ceRNAs) to regulate target gene expression and participate in tumorigenesis. However, the role of circRNA-mediated ceRNAs in bladder cancer (BC) remains unknown. Accordingly, the aim of this study was to elucidate the regulatory mechanisms in BC based on construction of the ceRNA network.MethodsThe RNA expression profiles were obtained from public datasets in the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database, and were used to establish a circRNA-miRNA-mRNA network. The interactions among proteins were analyzed using the STRING database and hubgenes were extracted using the cytoHubba application. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of differentially expressed mRNAs in BC and normal tissue samples were performed to determine the functions of the intersecting mRNAs.ResultsA total of 27 circRNAs, 76 miRNAs, and 4744 mRNAs were found to be differentially expressed between BC and normal tissues. The circRNA-miRNA-mRNA ceRNA network was established based on 21 circRNAs, 14 miRNAs, and 150 mRNAs differentially expressed in BC. We also established a protein-protein interaction network and identified 10 hubgenes, which were used to construct circRNA-miRNA-hubgene regulatory modules. The most enriched biological process GO term was strand displacement (P<0.05), and the homologous recombination and Fanconi anemia pathways were significantly enriched (P<0.05) for the differentially expressed genes in BC.ConclusionsWe screened several dysregulated circRNAs and established a circRNA-associated ceRNA network by bioinformatics analysis. The identified ceRNAs are likely critical in the pathogenesis of BC and may serve as future therapeutic biomarkers.
Highlights
Bladder cancer (BC) is one of the most commonly diagnosed genitourinary malignancies representing a major threat to public health [1]
A total of 27 circRNAs, 76 miRNAs, and 4744 mRNAs were found to be differentially expressed between bladder cancer (BC) and normal tissues
The identified competitive endogenous RNAs (ceRNAs) are likely critical in the pathogenesis of BC and may serve as future therapeutic biomarkers
Summary
Bladder cancer (BC) is one of the most commonly diagnosed genitourinary malignancies representing a major threat to public health [1]. Leonardo Salmena et al [11] proposed the competitive endogenous RNA (ceRNA) hypothesis in 2011, which posits that a complex post-transcriptional regulatory network of circRNAs can function as a microRNA(miRNA) sponge by complementary base pairing with targeted miRNA using miRNA response elements, thereby inhibiting the activity of miRNAs in regulating the expression of their downstream target genes to contribute to multiple malignancies. Supporting this hypothesis, Wu et al demonstrated that CEP128 acts as a ceRNA to regulate SOX11 expression by sponging miR-145-5p, thereby reducing its inhibitory effect of miR-145-5p on SOX11 in BC [12].
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