Circular RNA mediated gene regulation in human breast cancer: A bioinformatics analysis

by Giulia Fiscon, Alessio Funari, Paola Paci

Circular RNAs (circRNAs) are a new acknowledged class of RNAs that has been shown to play a major role in several biological functions both in physiological and pathological conditions, operating as critical part of regulatory processes, like competing endogenous RNA (ceRNA) networks. The ceRNA hypothesis is a recently discovered molecular mechanism that adds a new key layer of post-transcriptional regulation, whereby various types of RNAs can reciprocally influence each other’s expression competing for binding the same pool of microRNAs, even affecting disease development. In this study, we build a network of circRNA-miRNA-mRNA interactions in human breast cancer, called CERNOMA, that is a bipartite graph with one class of nodes corresponding to differentially expressed miRNAs (DEMs) and the other one corresponding to differentially expressed circRNAs (DEC) and mRNAs (DEGs). A link between a DEC (or DEG) and DEM is placed if it is predicted to be a target of the DEM and shows an opposite expression level trend with respect to the DEM. Within the CERNOMA, we highlighted an interesting deregulated circRNA-miRNA-mRNA triplet, including the up-regulated hsa_circRNA_102908 (BRCA1 associated RING domain 1), the down-regulated miR‐410-3p, and the up-regulated ESM1, whose overexpression has been already shown to promote tumor dissemination and metastasis in breast cancer.