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Cancer Cells and Metastasis · Journal article
Frontiers in Cell and Developmental Biology · August 14, 2026
Raises a question worth testing. It does not answer one.
This is a mechanistic discovery study proposing that a microRNA cluster (miRNAs 7, 17, 155) is associated with high-grade breast tumor dedifferentiation and EGFR-driven epithelial-mesenchymal transition. The findings are based on transcriptomic reanalysis and single-cell profiling without experimental validation of causality or clinical outcome data, and therefore represent a hypothesis-generating contribution suitable for hypothesis testing in future work.
Mechanistic exploratory study combining reanalysis of microarray data with single-cell RNA sequencing and spatial transcriptomic analysis. Breast cancer tissue samples stratified by histological grade (well-, moderately-, and undifferentiated/high-grade); specific patient enrollment and eligibility criteria not stated. Intervention: None; observational analysis of existing transcriptomic datasets and tissue samples. Compared with: Comparison of miRNA and mRNA expression across tumor grades; well- and moderately-differentiated tumors contrasted with high-grade tumors.
miRNAs 7, 17, and 155 were significantly upregulated in undifferentiated high-grade tumors High-grade tumors showed marked activation of EGFR-mediated epithelial-mesenchymal transition and elevated histological EGFR levels Single-cell RNA sequencing revealed a stem cell-like population characterized by the miRNA cluster 7/17/155 and EGFR-associated EMT activation
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If confirmed experimentally and clinically, the miRNA cluster 7/17/155 could serve as a molecular biomarker for breast tumor differentiation status and a therapeutic target. However, this remains exploratory and requires functional validation and prospective clinical studies before translation.
Mechanistic exploratory study using reanalysis of existing microarray data and single-cell sequencing to propose a miRNA cluster as a driver of breast tumor dedifferentiation; no clinical outcome or intervention trial conducted.
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If confirmed experimentally and clinically, the miRNA cluster 7/17/155 could serve as a molecular biomarker for breast tumor differentiation status and a therapeutic target. However, this remains exploratory and requires functional validation and prospective clinical studies before translation.
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Background 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). Methods 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. Results 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. Conclusion 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.
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