Integrative Bioinformatics Analysis of hsa-miR-21 in Breast Cancer Reveals a Prognostic Hub-Gene Signature

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-protein 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-Meier 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.

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Journal
International Journal of Molecular Sciences
Published
2026-01-15
DOI
https://doi.org/10.3390/ijms27020865
Primary Topic
MicroRNA in disease regulation
Type
article
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article

Integrative Bioinformatics Analysis of hsa-miR-21 in Breast Cancer Reveals a Prognostic Hub-Gene Signature

Saverio Sabina, Maria Rosaria Tumolo, Elisabetta De Matteis, Roberto Guarino et al.
International Journal of Molecular Sciences
MicroRNA in disease regulation
article

Integrative Bioinformatics Analysis of hsa-miR-21 in Breast Cancer Reveals a Prognostic Hub-Gene Signature

Saverio Sabina, Maria Rosaria Tumolo, Elisabetta De Matteis, Roberto Guarino, Luana Conte, Ugo De Giorgi
article en

Abstract

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-protein 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-Meier 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.

International Journal of Molecular SciencesVol. 27(2)
University of Salento (IT), Istituto Nazionale di Fisica Nucleare, Sezione di Lecce (IT), Institute for Research on Population and Social Policies (IT), Ospedale Vito Fazzi (IT), National Research Council (IT), University of Palermo (IT)
Good health and well-being
Openalex Percentile: Top 87%
MicroRNA in disease regulation
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