{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,31]],"date-time":"2025-08-31T11:10:02Z","timestamp":1756638602469,"version":"3.44.0"},"reference-count":0,"publisher":"Maad Rayan Publishing Company","content-domain":{"domain":["apb.tbzmed.ac.ir"],"crossmark-restriction":false},"short-container-title":["Adv Pharm Bull"],"abstract":"<jats:p>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 \u2014 microRNA-181a-2 \u2014 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: MTT-assay, transient transfection, lentiviral infection, qRT-PCR, immunoblotting, and reporter assay. 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\u2013induced resistance and demonstrated its role in the formation of an autoregulatory loop of miR-181a-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.<\/jats:p>","DOI":"10.34172\/apb.025.43440","type":"journal-article","created":{"date-parts":[[2025,8,31]],"date-time":"2025-08-31T10:33:12Z","timestamp":1756636392000},"update-policy":"https:\/\/doi.org\/10.34172\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["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 resistance"],"prefix":"10.34172","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6015-6619","authenticated-orcid":true,"given":"Olga Evgenievna","family":"Andreeva","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1264-7405","authenticated-orcid":true,"given":"Danila Vladimirovich","family":"Sorokin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1615-3928","authenticated-orcid":true,"given":"Svetlana Vladimirovna","family":"Vinokurova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2078-4274","authenticated-orcid":true,"given":"Pavel Borisovich","family":"Kopnin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0503-6016","authenticated-orcid":true,"given":"Nadezhda Viacheslavovna","family":"Elkina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4793-6063","authenticated-orcid":true,"given":"Danila Sergeevich","family":"Elkin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8813-7516","authenticated-orcid":true,"given":"Maria Dmitrievna","family":"Fedorova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2974-9555","authenticated-orcid":true,"given":"Alexander Mikhailovich","family":"Scherbakov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5902-7633","authenticated-orcid":true,"given":"Mikhail Aleksandrovich","family":"Krasil\u2019nikov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"20123","published-online":{"date-parts":[[2025,8,26]]},"container-title":["Advanced Pharmaceutical Bulletin"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/apb.tbzmed.ac.ir\/Inpress\/apb-43440.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/apb.tbzmed.ac.ir\/Inpress\/apb-43440.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,31]],"date-time":"2025-08-31T10:33:22Z","timestamp":1756636402000},"score":1,"resource":{"primary":{"URL":"https:\/\/apb.tbzmed.ac.ir\/Inpress\/apb-43440"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,26]]},"references-count":0,"URL":"https:\/\/doi.org\/10.34172\/apb.025.43440","relation":{},"ISSN":["2228-5881","2251-7308"],"issn-type":[{"value":"2228-5881","type":"print"},{"value":"2251-7308","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,26]]},"assertion":[{"value":"Tabriz University of Medical Sciences","name":"journal_owner","label":"Journal Owner"},{"value":"Tabriz University of Medical Sciences","name":"journal_publisher","label":"Journal Publisher"},{"value":"2024-07-28","order":1,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}