miR-30c-2-3p Regulates METTL14 Expression and Inhibits Cell Migration in Breast Cancer


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Emrence Z., Punar S., Zarerajabi V., Uslu S., Abaci N., Ekmekci S.

CURRENT ISSUES IN MOLECULAR BIOLOGY, cilt.48, sa.6, 2026 (SCI-Expanded, Scopus)

Özet

Breast cancer remains a leading cause of cancer-related mortality worldwide, with epigenetic mechanisms like N-6 methyladenosine (m(6)A) modification playing a crucial role in tumorigenesis. The interaction between microRNAs and m(6)A regulators, such as the methyltransferase METTL14, is increasingly recognized as a key pathway in oncogenesis. This study investigated whether miR-30c-2-3p regulates METTL14 expression to influence global m(6)A levels and cell migration in breast epithelial (MCF12A) and breast cancer (MCF7) cell lines. Following transfection with miR-30c-2-3p mimics, successful overexpression was confirmed in both cell lines. Subsequent RT-qPCR and Western blotting analyses demonstrated that METTL14 mRNA and protein levels were significantly reduced at 24 and 48 h post-transfection (p < 0.05). Concurrently, global m(6)A RNA methylation levels decreased, with a more pronounced reduction observed in MCF12A cells (p < 0.001). Functionally, wound healing assays revealed that miR-30c-2-3p significantly inhibited migration, reducing wound closure by 30-44% in MCF7 cells and by 66-72% in MCF12A cells. These findings reveal a novel regulatory axis involving miR-30c-2-3p, METTL14, and m(6)A, suggesting that miR-30c-2-3p functions as a tumor suppressor and represents a promising biomarker and therapeutic target in breast cancer.