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Bioinformatics Analysis of microRNAs Associated with Metastatic Potential in Breast Cancer
by
, , ,
Aleksandra Nikezić
1, 
Sanja Goč
2,
Jovana Stevanović
2,
Miloš Brkušanin
3,
Olgica Nedić
2,
Jovana Jovankić
1 and
Zorana Dobrijević
2,* 1
Department of Biology and Ecology, Faculty of Science, University of Kragujevac, 34000 Kragujevac, Serbia
2
Institute for the Application of Nuclear Energy, University of Belgrade, 11080 Belgrade, Serbia
3
Centre for Human Molecular Genetics, Faculty of Biology, University of Belgrade, 11158 Belgrade, Serbia
*
Author to whom correspondence should be addressed.
Biology 2026, 15(8), 617; https://doi.org/10.3390/biology15080617
Submission received: 12 March 2026
/
Revised: 30 March 2026
/
Accepted: 9 April 2026
/
Published: 14 April 2026
(This article belongs to the Special Issue Non-Coding RNA Research and Functional Insights)
Simple Summary
Key microRNA players that are relevant for breast cancer aggressiveness, with crucial roles in mediating cancer migration, epithelial–mesenchymal transition, invasion and metastasis, remain underexplored. Therefore, we aimed to address this issue and uncover the potential candidate microRNAs associated with the metastatic potential of breast cancer by employing an in silico approach. We combined data from microRNA profiling studies to identify a minimal set of dysregulated microRNAs and to bioinformatically characterize their potential functional properties. Five microRNAs emerged as plausible cancer aggressiveness-associated regulators, one of which displayed distinctive pro-metastatic properties, while three downregulated microRNAs were significantly associated with negative clinical features, and their targets were enriched with genes that were relevant for cancer’s aggressiveness. These results are consistent with the presumed functional relevance of selected DE-microRNAs in BC and hold their value for future investigations focusing on biomarker discovery, improvements in diagnosis, outcome prediction, decision-making and treatment monitoring, as well as for enhancing therapeutic effectiveness.
Abstract
Dysregulation of microRNA expression in breast cancer (BC) has been associated with molecular disturbances involved in cancer initiation, progression and metastasis. Specific microRNAs also act as endocrine modulators in BC, thereby influencing the biological behavior of the tumor and drug responses. Our objective was to employ bioinformatics tools to identify and characterize microRNAs acting as candidate players involved in epithelial–mesenchymal transition, migration, invasion, and/or hormonal regulation in BC. We systematically integrated microRNA profiling data from three different studies on BC cell lines with different invasive capabilities and from another study on lymph node metastases and matching primary BC, resulting in five microRNA hits—DE-microRNAs miR-146a-5p, miR-222-3p, miR-205-5p, miR-141-3p and miR-200c-3p. This set of microRNAs was evaluated for clinical significance in BC and subjected to target prediction, microRNA–mRNA network construction, functional enrichment analysis and quantification in BC cell lines by qPCR. An upregulated DE-microRNA, miR-222-3p, displayed distinctive pro-metastatic features, supported by its clinical relevance, as well as by the results of the functional enrichment analysis of its target genes. Downregulation of the members of the miR-200 family and miR-205-5p were significantly associated with negative clinical features, while their targets were enriched with genes that were relevant to cancer aggressiveness. These results are in line with the presumed functional relevance of the selected DE-microRNAs in BC.
