{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T03:44:31Z","timestamp":1784346271317,"version":"3.55.0"},"reference-count":45,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Breast cancer (BC) is the most frequently diagnosed malignancy in women and remains a leading cause of cancer-related mortality worldwide. Among the oncogenic microRNAs, hsa-miR-21 has been consistently implicated in tumorigenesis, yet a comprehensive network-level understanding of its regulatory landscape in BC is lacking. In this study, we performed an integrative bioinformatics analysis to characterize the molecular pathways and prognostic impact of hsa-miR-21. Experimentally validated mRNA targets were retrieved from miRTarBase and used to construct a high-confidence protein\u2013protein interaction network via STRING, followed by hub-gene prioritization in Cytoscape. Functional enrichment analyses were conducted with DAVID to assess Gene Ontology (GO) categories and KEGG pathways. Survival analyses were performed in large BC cohorts from METABRIC and TCGA using the Kaplan\u2013Meier Plotter. We identified 12 hub genes that are central regulators of apoptosis, proliferation, immune signaling, and transcriptional control. GO and KEGG analyses revealed enrichment in cancer-related, immune, and metabolic pathways, underscoring the pleiotropic role of miR-21. While miR-21 expression alone was not significantly associated with overall survival, a composite hub-gene signature demonstrated strong prognostic value. These findings highlight the importance of network-level biomarkers in BC and provide a reproducible framework for dissecting the clinical relevance of disease-associated miRNAs.<\/jats:p>","DOI":"10.3390\/ijms27020865","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T12:31:41Z","timestamp":1768480301000},"page":"865","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrative Bioinformatics Analysis of hsa-miR-21 in Breast Cancer Reveals a Prognostic Hub-Gene Signature"],"prefix":"10.3390","volume":"27","author":[{"given":"Maria Rosaria","family":"Tumolo","sequence":"first","affiliation":[{"name":"Institute for Research on Population & Social Policies, Research Unit of Brindisi, National Research Council, 72100 Brindisi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luana","family":"Conte","sequence":"additional","affiliation":[{"name":"Department of Physics and Chemistry \u201cE. Segr\u00e8\u201d, University of Palermo, 90128 Palermo, Italy"},{"name":"Advanced Data Analysis in Medicine (ADAM), Laboratory of Interdisciplinary Research Applied to Medicine (DReAM), Local Health Authority (ASL) of Lecce, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0127-6557","authenticated-orcid":false,"given":"Roberto","family":"Guarino","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology, Branch of Lecce, National Research Council, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ugo","family":"De Giorgi","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Salento, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0150-780X","authenticated-orcid":false,"given":"Elisabetta","family":"De Matteis","sequence":"additional","affiliation":[{"name":"Oncology Unit, \u2018Vito Fazzi\u2019 Hospital, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saverio","family":"Sabina","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology, Branch of Lecce, National Research Council, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,15]]},"reference":[{"key":"ref_1","unstructured":"(2025, October 01). 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