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Continuous uptake of miR-181a-2 mimetic induces constitutive overexpression of cellular miR-181a-2 in MCF-7 breast cancer cells: links with progression of drug resistanceстатья Исследовательская статья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 23 января 2026 г.
- Авторы: Andreeva O.E., Sorokin D.V., Vinokurova S.V., Kopnin P.B., Elkina N.V., Elkin D.S., Fedorova M.D., Scherbakov A.M., Krasil’nikov M.A.
- Журнал: ADVANCED PHARMACEUTICAL BULLETIN
- Том: 15
- Номер: 3
- Год издания: 2025
- Первая страница: 678
- Последняя страница: 685
- DOI: 10.34172/apb.025.43440
- Аннотация: Purpose: The aim of this study was to elucidate the mechanisms underlying the formation and maintenance of drug resistance in cancer cells. Previously, we demonstrated that prolonged treatment of estrogen-dependent MCF-7 breast cancer cells with exosomes derived from estrogen-resistant MCF-7/T cells leads to a partial loss of estrogen sensitivity in MCF-7 cells. Moreover, repeated transfection with one of the exosomal microRNAs—microRNA-181a-2—induced an irreversible decrease in hormonal sensitivity in the recipient cells. In the present work, to further investigate the possible mechanism of miR-181a-2-induced acquired resistance, we analyzed the effect of multiple miR-181a-2 transfections on the expression of cellular miR-181a-2 and related signaling proteins.Methods: miR-181a-2 was ectopically expressed by mimetic transfection or suppressed by antisense oligonucleotides. miR-181a-2 precursor/MIR181A2HG expression (qRT-PCR) and MIR181A2 locus copy number (qPCR) were assessed. wtSnail was expressed via transient transfection. Tamoxifen sensitivity was measured by MTT assay. Protein expression was studied by immunoblotting, estrogen receptor α/Snail transcriptional activity was evaluated by reporter analysis.Results: We found that multiple transfections with miR-181a-2 resulted in a marked increase in cellular miR-181a-2 precursor levels, whereas single transfection had no such effect. Similarly, stable transfection with miR-181a-2 led to increased levels of cellular miR-181a-2 and its host gene, MIR181A2HG, which was associated with partial resistance to tamoxifen. Analysis of the genomic DNA encoding miR-181a-2 revealed no changes in copy number in transfected cells. Furthermore, we identified the transcription factor Snail as a key mediator of miR-181a-2–induced resistance and demonstrated its role in the formation of an autoregulatory loop of miR181a-2 and the maintenance of cell resistance.Conclusion: Overall, these results reveal a novel mechanism of resistance-associated signaling pathway rearrangement based on the formation of a miR-181a-2 autoregulatory loop.
- Добавил в систему: Андреева Ольга Евгеньевна
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