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

Sep 21, 2026

Although the miR-183/182/96 cluster is overexpressed in breast cancer, its function in pre-carcinogenic early lesions with disrupted adherens junctions (AJ) has remained unclear. Using microRNA and RNA sequencing data from The Cancer Genome Atlas (TCGA) Breast Cancer project, the study links cluster dysregulation to AJ signaling. All cluster members are overexpressed in early-stage disease; AJ pathway genes down-regulated in early-stage cancer are enriched for experimentally validated miR-183/182/96 targets. hsa-miR-182 inversely correlates with WASF3, EGFR, MET, and CTNNA3, while later-stage oncogenic shifts are suggested.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Background and Rationale

miR-183/182/96 cluster in breast cancer

Non-coding RNAs and microRNA mechanism

Early-Stage Cancer and Cell-Cell Communication

Adherens junctions and disrupted intercellular signaling

MicroRNAs and epithelial phenotype changes

Study Design and Findings

TCGA-based microRNA and RNA sequencing analysis

AJ pathway enrichment and validated targets

hsa-miR-182 inverse correlations

Interpretation and Implications

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Investigating the interplay between the mir-183/182/96 cluster and the adherens junction pathway in early-stage breast cancer Tala Noun1, Abdallah Kurdi2, Nour Maatouk1, Rabih Talhouk1􀀍 & Heinrich zu Dohna1􀀍 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 ofthe 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. According to the World Health Organization, breast cancer (BC) is the most commonly occurring cancer worldwide. In women, it is the most diagnosed cancer and the leading cause of cancer-related deaths1. Therefore, a better understanding of the etiology of BC is needed. Most BCs are triggered by lifestyle and environmental factors2 which can induce DNA damage and some acquired mutations are also capable of altering the epigenome. Non-coding RNAs (ncRNAs) are epigenetic regulators whose expression is often highly altered in cancer3,4. Given their roles in fine-tuning gene expression and their involvement in a number of cellular processes, ncRNAs can alter normal cell function. MicroRNAs are short ncRNAs whose most well-described role is to post-transcriptionally modulate gene expression by binding to the 3’UTR of their designated mRNA targets, destabilizing the mRNAs and inhibiting their translation. Because microRNAs are released into the bloodstream and can be easily retrieved from body fluids, they are promising agents for the diagnosis, prevention, and treatment of several diseases5. Tens of microRNAs are deregulated in BC, including the miR-183/182/96 cluster which is a group of genes encoding microRNAs 183, 182, and 96. Members of the miR-183/182/96 cluster are generally overexpressed in cancer6. In fact, the cluster is upregulated in BC tissue and cell lines as compared to normal counterparts7. ThemiR-183/182/96 cluster is implicated in a number of BC hallmarks such as proliferation, migration, invasion, angiogenesis, etc8–10. However, little is known about the role of these microRNAs during the early stages of BC development. Early stages of cancer development are associated with a deregulation of intercellular communication, either through changes in the expression levels of proteins injunctional complexes and/or changes in their distribution. Previous work from our lab showed the importance of intercellular communication via gap junctional complexes in the differentiation of ductular and alveolar mammary epithelial cells. The inhibition of gap junctional intercellular communication in alveolar mammary epithelial CID-9 cells disrupted the production of β-casein – a marker of alveolar cell differentiation11. Similarly, knocking down connexin-43 (Cx43), a gap junctional protein, in non-neoplastic HMT-3522 S1 ductular mammary epitheli

FAQs

What is the main question of the study?

The study investigates how the miR-183/182/96 microRNA cluster relates to adherens junction (AJ) signaling during early-stage breast cancer development.

How was the relationship between the miR-183/182/96 cluster and AJ signaling tested?

MicroRNA and RNA sequencing data from The Cancer Genome Atlas (TCGA) Breast Cancer project were used to assess pathway enrichment and target relationships.

Which targets show an inverse correlation with hsa-miR-182?

hsa-miR-182 inversely correlates with mRNA expression of WASF3, EGFR, MET, and CTNNA3, which belong to the AJ signaling pathway.

Sep 21, 2026

Uploaded by River Wang