CircRNA-associated ceRNA network reveals ERBB and Hippo signaling pathways in hypopharyngeal cancer

Abstract

Accumulating evidence has suggested that circular RNAs (circRNAs), a novel class of non-coding RNAs, have crucial roles in tumor progression. However, the significance of circRNAs in hypopharyngeal cancer (HCa) remains to be investigated. The present study has identified aberrantly expressed circRNAs by performing circRNA sequencing analyses of three pairs of tumor and adjacent normal samples from patients with HCa. The results demonstrated that 173 circRNAs were differentially expressed (DE), including 71 upregulated and 102 downregulated circRNAs (FDR<0.05 and fold changes of ≥2 or ≤0.5 by Mann-Whitney U test followed by Benjamini-Hochberg correction for multiple testing). Pathway analyses of the genes producing DE circRNAs revealed that many of them were involved in cancer-related pathways. To further illustrate the roles of circRNAs in HCa progression, a competing endogenous RNA (ceRNAs) network was constructed, consisting of circRNAs, miRNA, and miRNA targeted genes. The results demonstrated that multiple cancer-related pathways were affected by performing enrichment analyses of the targeted genes. Of note, a ceRNA subnetwork was isolated, consisting of two circRNAs (has-circ-0008287 and has-circ-0005027) and one miRNA (hsa-miR-548c-3p), which significantly affect both ERBB and Hippo signaling pathways. In conclusion, the present study identified a set of circRNAs that are potentially implicated in the tumorigenesis of HCa and may serve as potential biomarkers for the diagnosis of HCa.