Integrated whole transcriptome profiling of circRNAs reveals a convoluted crosstalk in competing endogenous RNAs regulatory network in Colorectal Cancer

Abstract Recently it has been identified that circRNAs can act as miRNAs sponge to regulate gene expression in various types of cancers to associate with cancer initiation and progression. The present study aims to identify colorectal cancer-related circRNAs and the underpinning mechanisms of circRNA/miRNA/mRNA networks in the development and progress of Colorectal Cancer. Differentially expressed circRNAs, miRNAs, and mRNAs were identified in GEO microarray datasets using the Limma package of R. Differentially expressed circRNAs analysis resulted in 23 upregulated and 31 downregulated circRNAs. CeRNAs networks were constructed by intersecting the results of predicted and experimentally validated databases, circbank and miRWalk, and DEMs and DEGs analysis using Cytoscape. Then, the functional enrichment analysis was performed for DEGs included in ceRNA networks. Followed by survival analysis, expression profile validation using TCGA and GEO data, and ROC curve analysis we reached a ceRNA sub-networks which revealed the potential regulatory effect of hsa_circ_0001955 and hsa_circ_0071681 on the survival-related genes, KLF4, MYC, CCNA2, RACGAP1, and CD44. Overall, we constructed a convoluted regulatory network and the likely mechanisms of its action in CRC, which may contribute to developing more effective approaches for early diagnosis, prognosis, and treatment of CRC.