{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T03:45:12Z","timestamp":1784346312006,"version":"3.55.0"},"reference-count":47,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T00:00:00Z","timestamp":1736985600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of General Medical Sciences of the National Institutes of Health","award":["R16GM153947"],"award-info":[{"award-number":["R16GM153947"]}]},{"name":"National Institute of General Medical Sciences of the National Institutes of Health","award":["R16GM145561"],"award-info":[{"award-number":["R16GM145561"]}]},{"name":"NIH\/NIGMS","award":["R16GM153947"],"award-info":[{"award-number":["R16GM153947"]}]},{"name":"NIH\/NIGMS","award":["R16GM145561"],"award-info":[{"award-number":["R16GM145561"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Breast cancer treatment has advanced significantly, particularly for estrogen receptor-positive (ER+) tumors. Tamoxifen, an estrogen antagonist, is widely used; however, approximately 40% of patients develop resistance. Recent studies indicate that microRNAs, especially miR-155, play a critical role in this resistance. Our analysis of MCF-7 tamoxifen-sensitive (TAM-S) and tamoxifen-resistant (TAM-R) cells revealed that miR-155 is significantly upregulated in TAM-R cells. Overexpression of miR-155 in TAM-S cells increased resistance to tamoxifen. Additionally, genistein, a natural isoflavone from soybeans, effectively downregulated miR-155 and its targets associated with apoptosis and glucose metabolism, including STAT3 and hexokinase 2 (HK2). Notably, genistein also significantly decreased cell migration, suggesting potential anti-metastatic effects. Furthermore, genistein reduced glucose consumption, indicating its potential to overcome miR-155-mediated tamoxifen resistance and modulate the Warburg effect. These findings highlight genistein as a promising therapeutic agent for overcoming tamoxifen resistance in ER+ breast cancer and merit further investigation.<\/jats:p>","DOI":"10.3390\/ijms26020733","type":"journal-article","created":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T09:58:36Z","timestamp":1737021516000},"page":"733","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Soy Isoflavone Genistein Enhances Tamoxifen Sensitivity in Breast Cancer via microRNA and Glucose Metabolism Modulation"],"prefix":"10.3390","volume":"26","author":[{"given":"Jessica","family":"Shpigel","sequence":"first","affiliation":[{"name":"Department of Chemistry, Herbert H. Lehman College, City University of New York, New York, NY 10468, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9787-1300","authenticated-orcid":false,"given":"Emilia F.","family":"Luciano","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Herbert H. Lehman College, City University of New York, New York, NY 10468, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blessing","family":"Ukandu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Herbert H. Lehman College, City University of New York, New York, NY 10468, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2710-3491","authenticated-orcid":false,"given":"Moira","family":"Sauane","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Herbert H. Lehman College, City University of New York, New York, NY 10468, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5438-8157","authenticated-orcid":false,"given":"Columba","family":"de la Parra","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Herbert H. Lehman College, City University of New York, New York, NY 10468, USA"},{"name":"Biochemistry, Biology, and Chemistry Ph.D. Programs, The Graduate Center, City University of New York, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Mitaishvili, E., Feinsod, H., David, Z., Shpigel, J., Fernandez, C., Sauane, M., and de la Parra, C. (2024). The Molecular Mechanisms behind Advanced Breast Cancer Metabolism: Warburg Effect, OXPHOS, and Calcium. Front. Biosci. 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