{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T06:27:17Z","timestamp":1786688837687,"version":"build-2736575974"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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\u2013miRNA 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2026.1899163","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T05:33:16Z","timestamp":1786685596000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["MicroRNA cluster 7\/17\/155 as a potential driver for high-grade breast tumors transformation through EGFR-associated EMT"],"prefix":"10.3389","volume":"14","author":[{"given":"Saeed","family":"Khodayari","sequence":"first","affiliation":[{"name":"Breast Disease Research Center, Cancer Institute of Iran, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences","place":["Tehran, Iran"]},{"name":"Department of Animal Biology, Faculty of Biological Sciences, Kharazmi 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