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

TL;DR

This study explores the role of hsa-miR-21 in breast cancer and identifies a set of key genes that could help predict patient outcomes.

Contribution

The study introduces a network-based approach to identify a prognostic hub-gene signature linked to hsa-miR-21 in breast cancer.

Findings

12 hub genes were identified as central regulators in apoptosis, proliferation, immune signaling, and transcriptional control.

Functional analyses showed enrichment in cancer-related, immune, and metabolic pathways.

A composite hub-gene signature showed strong prognostic value, even though miR-21 alone did not predict survival.

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.

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