Integrative in silico analysis suggests miR-152-3p as a potential regulator of DNMT1 in breast cancer, with implications for triple-negative breast cancer
Abstract
Aims: Epigenetic dysregulation plays a critical role in cancer initiation, progression, and therapeutic resistance. Among epigenetic mechanisms, DNA methylation—primarily maintained by DNA methyltransferase 1 (DNMT1)—is frequently altered in cancer, including triple-negative breast cancer (TNBC). This study aimed to systematically identify DNMT1-targeting microRNAs (miRNAs) and evaluate their potential regulatory roles using an integrative in silico approach.
Methods: DNMT1-targeting miRNAs were identified using TargetScan, DIANA-microT, and miRDB. Candidate miRNAs were further evaluated through an integrative multi-step analysis, including transcription factor and Gene Ontology (GO) enrichment analyses performed using the Enrichr platform, expression profiling and survival analysis using UALCAN, DNMT1 expression analysis across breast cancer subtypes using GEPIA2, and co-expression analysis using the ENCORI (starBase) platform.
Results: Four candidate miRNAs were identified as potential regulators of DNMT1. Expression and survival analyses indicated that hsa-miR-148b-3p is significantly upregulated in breast cancer (p = 1.62 × 10⁻¹²) and associated with poorer survival (p = 0.04), whereas hsa-miR-152-3p showed no significant association with expression or survival (p > 0.05). DNMT1 expression was consistently elevated across breast cancer subtypes, including basal-like tumors. Co-expression analysis revealed that only hsa-miR-152-3p demonstrated a statistically significant inverse correlation with DNMT1 expression (r = −0.159, p = 1.51 × 10⁻⁷), suggesting a potential post-transcriptional regulatory relationship. Functional enrichment analyses indicated that DNMT1-associated miRNAs are involved in transcriptional regulation, intracellular signaling pathways—including PI3K/AKT, Wnt, and TGF-β—and epithelial–mesenchymal transition (EMT)-related processes.
Conclusion: This integrative analysis suggests that DNMT1 regulation in breast cancer is selectively associated with specific miRNAs rather than broadly mediated by multiple candidates. Among the evaluated miRNAs, miR-152-3p emerged as the most consistent potential regulator of DNMT1, while miR-148b-3p appeared more closely associated with clinical outcomes. These findings highlight the potential relevance of the DNMT1–miRNA regulatory axis and provide a focused bioinformatic framework for future experimental studies investigating DNMT1–miRNA interactions, particularly in TNBC.
Keywords
References
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Details
Primary Language
English
Subjects
Medical Genetics (Excl. Cancer Genetics)
Journal Section
Research Article
Authors
Asuman Özgöz
*
0000-0003-4018-5807
Türkiye
Publication Date
June 16, 2026
Submission Date
February 15, 2026
Acceptance Date
June 3, 2026
Published in Issue
Year 2026 Volume: 6 Number: 2