Abstract
BackgroundCircular RNAs (circRNAs) have emerged as potential clinical targets in cancer therapy, since they have been shown to play a crucial role in tumor development by acting as competitive endogenous RNAs (ceRNAs) that regulate downstream mRNA expression by sequestering microRNAs (miRNAs). The present study, aimed to identify novel ceRNA networks involving circRNAs, miRNAs, and mRNAs in using a combination of Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets and explore the function of circ_0000518 in the malignancy of colorectal cancer (CRC). MethodsRaw data related to CRC, including circRNAs, miRNAs and mRNAs, were downloaded from GEO and TCGA databases. A circRNA/miRNA/mRNA network was established by differential analysis and multiple databases were used to predict downstream targets. The role of this network in the development of CRC was further validated by a series of cellular experiments including dual luciferase assay, migration assay and flow apoptosis assay. ResultsDifferential expression analysis of two GEO datasets (GSE142837 and GSE126094) revealed four circRNAs, which were used to predict downstream miRNAs and mRNAs based on several databases. These predictions, combined with TCGA analysis, were used to construct a ceRNA network composed of 4 circRNAs, 9 miRNAs, and 52 mRNAs. The circ_0000518/miR-326/ephrin type-B receptor 3 (EPHB3) axis was eventually selected for functional validation in two CRC cell lines. Subsequently, it was experimentally verified that circ_0000518 was highly expressed in CRC; meanwhile, it was found that the proliferation and migration of CRC cells were significantly weakened by knocking down circ_0000518, while apoptosis of tumors was promoted. ConclusionThe data demonstrated the identification of a novel circRNA/miRNA/mRNA competitive endogenous network in CRC. The regulatory role of the circ_0000518/miR-326/EPHB3 axis in this network was preliminarily validated by cellular experiments exploring CRC tissue samples and two CRC cell lines.
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