Investigating the interplay between the mir-183/182/96 cluster and the adherens junction pathway in early-stage breast cancer.

Abstract

Although the miR-183/182/96 cluster is overexpressed in breast cancer (BC), little is known about its role in the development of pre-carcinogenic lesions which harbor disrupted adherens junctions (AJ) and may promote BC. Here, we used microRNA and RNA sequencing data from The Cancer Genome Atlas (TCGA) Breast Cancer project to investigate the relationship between the miR-183/182/96 cluster and AJ signaling in early-stage BC. We found that all members of the cluster are significantly overexpressed in early-stage BC, the AJ signaling pathway is enriched for genes down-regulated in early-stage BC, and the AJ signaling pathway is enriched for experimentally validated targets of the miR-183/182/96 cluster. The expression of hsa-miR-182 correlates inversely with the mRNA expression of four of its target genes belonging to the AJ signaling pathway: WASF3, EGFR, MET, and CTNNA3. However, the correlations between hsa-miR-182 and AJ gene expression did not differ significantly between targets and non-targets of hsa-miR-182. This suggests that regulatory effects of microRNAs are less pronounced in cancer, as has been shown by other studies. Furthermore, WASF3, EGFR, and MET are oncogenes that tend to be upregulated in later BC stages, implying that the role of some AJ genes changes with different BC stages.