Integrative miRNA–mRNA functional analysis identifies miR-182 as a potential prognostic biomarker in breast cancer

Abstract

Breast cancer (BC) is a heterogeneous disease distinct from major clinical hindrances, and microRNAs (miRNAs) have been accounted to partake in BC progression. Identifying potential miRNAs and their pathological significance in BC could pave the way for precisely targeted treatments. This study exploits transcriptomic BC miRNA, mRNA cohorts, and prognostic significance via an integrative functional approach. miRNA transcriptomic cohorts (GSE45666, GSE40267, and GSE19783) were utilized to disseminate differentially expressed miRNAs (DEmiRNAs) and their expression in the clinicopathological variables of BC. miR-182 was identified as a potent candidate, differentially expressed between each BC stage and its adjacent normal samples. The expression of miR-182 was significantly associated with estrogen receptor (ER) (p = 0.052), and closely related to progesterone receptor (PR) (p = 0.061) and human epidermal growth factor receptor 2 (Her2) (p = 0.077). miRNA–mRNA regulatory targets were predicted using six different databases, namely, TargetScan, miRDB, Diana, miRNet, TargetMiner, and miRWalk. Twenty-four promising mRNA regulatory targets were potentially identified for miR-182 and thus highly enriched with cellular metabolic processes, proteoglycans, and focal adhesion pathways in the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms. Subsequently, the F-box and WD repeat domain containing 7, E3 ubiquitin protein ligase (FBXW7) gene was recognized as a hub with the highest connectivity score in the protein–protein interaction network. Furthermore, miR-182 and FBXW7 were associated with poor prognostic clinical outcomes in BC patients. Thus, our integrated functional analysis suggests that miR-182 might lead to a new therapeutic target in BC manifestation.