MicroRNA cluster 7/17/155 as a potential driver for high-grade breast tumors transformation through EGFR-associated EMT.

Authors

Saeed Khodayari, Hamid Khodayari, Hanieh Jalali, Elnaz Saeedi, Ahad Muhammadnejad, Mohammad Dashtkoohi, Amirnader Emami Razavi, Meghdad Yeganeh, Reza Shirkoohi, Seyed Rouhollah Miri, Ramesh Omranipour, Habibollah Mahmoodzadeh

Published in

Frontiers in cell and developmental biology. Volume 14. Pages 1899163. Epub Aug 14, 2026.

Abstract

Breast tumor dedifferentiation and progression onto high-grade states with stem-like fea-tures are governed by complex regulatory networks within the tumor microenvironment. This study aimed to identify a potential microRNA (miRNA) cluster associated with breast tumor stemness and in-vestigate its regulatory functions inspired by mammary gland development (MGD).
We reana-lyzed microarray data and identified differentially expressed mRNAs and miRNAs in breast cancer of various grades. High-throughput transcriptomic datasets were incorporated to strengthen the discovery framework. Spatial mRNA-miRNA interactions in each breast cancer grade were identified, and a series of q-PCR, immunohistochemical analysis of epidermal growth factor receptor (EGFR) expression, and Single-cell RNA sequencing were used to validate findings.
MGD-related regulatory mecha-nisms correlated with well- and moderately-differentiated tumors but were absent in high-grade tumors. miRNAs 7, 17, and 155 were significantly upregulated in undifferentiated high-grade tumors. These tu-mors also showed marked activation of EGFR-mediated epithelial-mesenchymal transition (EMT) and elevated histological EGFR levels. scRNA-seq revealed a stem cell-like and undifferentiated cellular pop-ulation characterized by miRNAs 7, 17, and 155, as well as EGFR-associated EMT activation. Pseudotemporal trajectory analysis indicated this cluster as a potential origin of malignant breast tumor heterogeneity and stemness.
The miRNA cluster 7/17/155 may act as a potential driver of breast tumor dedifferentiation and acquisition of stem-like properties via EGFR-mediated EMT. This cluster represents a promising target for therapies to reverse tumor dedifferentiation and a biomarker for molecular classification of breast tumor differentiation status.

PMID:
42666385
Bibliographic data and abstract were imported from PubMed on 29 Aug 2026.

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