Abstract

BackgroundCircular RNAs (circRNAs) have received considerable attention in human cancer research. However, many circRNAs remain to be detected. In our study, we determined novel circRNAs and investigated their effects on bladder cancer (BCa).MethodsMicroarray dataset GSE92675 was downloaded from Gene Expression Omnibus (GEO). Then, we combined computational biology with quantitative real-time polymerase chain reaction (qRT-PCR) to select related circRNAs in BCa. The selected circRNA–microRNA (miRNA)–messenger RNA (mRNA) regulatory subnetwork was determined by Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses.ResultsThe regulatory network constructed from the microarray dataset (GSE92675) contained 49 differentially expressed circRNAs (DECs). GO and KEGG analyses showed that the MAPK and PI3K–AKT signaling pathways were statistically significant. On the basis of qRT-PCR and the degree value calculated by the cytoHubba plugin of Cytoscape, hsa_circ_0011385 was finally confirmed. The subnetwork around hsa_circ_0011385 was constructed. In addition, we created a protein–protein interaction (PPI) network composed of 67 nodes and 274 edges after removing independent nodes. GO and KEGG analyses showed that hubgenes were involved in cell cycle activities. Moreover, they could be regulated by miRNAs and play an eventful role in BCa pathogenesis.ConclusionsWe proposed a novel circRNA–miRNA–mRNA network related to BCa pathogenesis. This network might be a new molecular biomarker and could be used to develop potential treatment strategies for BCa.

Highlights

  • Circular RNAs have received considerable attention in human cancer research

  • One of their molecular mechanisms is that they act as competing endogenous RNAs, which serve as microRNA sponges

  • Identification of hubgenes from the protein–protein interaction (PPI) network using the Molecular Complex Detection (MCODE) algorithm After obtaining the target genes of hsa_circ_0011385, we created a PPI network composed of 67 nodes and 274 edges (Fig. 12a)

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Summary

Introduction

Circular RNAs (circRNAs) have received considerable attention in human cancer research. Bladder cancer (BCa) has become the most commonly occurring cancer of the urinary system with high mortality rates worldwide [1] It is categorized into two types: Lu et al Cancer Cell Int (2020) 20:31. CircRNAs, which widely exist in eukaryotic cells with a covalently closed loop structure, were observed for the first time in 1976 [4]. They were misconceived as by-products of splicing errors due to the limitation of traditional RNA detection methods [5]. CircRNAs are involved in the initiation and progression of cancers One of their molecular mechanisms is that they act as competing endogenous RNAs (ceRNAs), which serve as microRNA (miRNA) sponges.

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