Investigation of circRNA-miRNA-mRNA network in colorectal cancer using an integrative bioinformatics approach

Identification of competing endogenous RNAs (ceRNAs), especially circRNAs, have become new hotspots in cancer researches. Although, their roles and underlying mechanisms in colorectal cancer (CRC) development remain mostly unknown. The aim of this study was to integrate both coding and non-coding available microarray data in development of CRC coupled with bioinformatics analyses to understand a more inclusive pathobiologic map regarding their molecular interactions and functions. Methods: The microarray data were retrieved from the Gene Expression Omnibus (GEO) database and analyzed. Several bioinformatics tools and databases including CircInteractome, CSCD, miRTarbBase, TargetScan, miRmap, GEPIA, STRING, Enrichr, DAVID, and MCODE were applied for further elucidation. Principal component analysis (PCA) has seperatly run for four datasets. The dysregulated circRNA-miRNA-mRNA network in CRC was constructed by Cytoscape. In addition, co-expression and protein-protein interaction (PPI) networks were established based on differentially expressed (DE) protein coding genes in CRC. Results: PCA discloses colorectal tumor and normal tissuses could be distinguished not only by mRNAs expression profile, but also by both circRNAs and miRNAs expression profiles. We identified 14 DE mRNAs (commonly between two datasets), 85 DE miRNAs and 36 DE circRNAs in CRC tissues compared with normal tissues. Taking their potential interactions into account, a circRNA-miRNA-mRNA network was constructed. Then, according to ceRNA hypothesis, the axes with expression in the desired direction were extracted. Our results disclosed some DE circRNAs with potential oncogenic (circ_0014879) or tumor suppressive (circ_0001666 and circ_0000977) effects. Finally, PPI network suggests pivotal roles for DOCK2 and PTPRC dysregulation in progression of CRC, possibly by facilitating of tumor escape from immune surveillance. Conclusion: Current study proposes a novel regulatory network consisting of DE circRNAs, miRNAs and mRNAs in CRC development that in turn highlights the roles of DE circRNAs at the upstream of oncotranscriptomic cascade in CRC development, suggesting their potentiality to be utilized as both prognostic and therapeutic biomarker.