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• W2756765053 abstract "Tamoxifen (TAM) is a major adjuvant therapy for patients who are diagnosed with estrogen receptor-α(ER)–positive breast cancer; however, TAM resistance occurs often during treatment and the underlying mechanism is unclear. Here, we report that miR-125a-3p inhibits ERα transcriptional activity and, thus, ER+ breast cancer cell proliferation, which causes cell-cycle arrest at the G1/S stage, inducing apoptosis and suppressing tumor growth by targeting cyclin-dependent kinase 3 (CDK3) in vitro and in vivo. In addition, CDK3 and miR-125a-3p expression levels were measured in 37 cancerous tissues paired with noncancerous samples, and their expression levels were negatively associated with miR-125a-3p level. Of interest, miR-125a-3p level is down-regulated in MCF-7 TAM-resistant (TamR) cells. Of more importance, up-regulation of miR-125a-3p resensitizes MCF-7 TamR cells to TAM, which is dependent on CDK3 expression. These results suggest that miR-125a-3p can function as a novel tumor suppressor in ER+ breast cancer by targeting CDK3, which may be a potential therapeutic approach for TamR breast cancer therapy.—Zheng, L., Meng, X., Li, X., Zhang, Y., Li, C., Xiang, C., Xing, Y., Xia, Y., Xi, T. miR-125a-3p inhibits ERα transactivation and overrides tamoxifen resistance by targeting CDK3 in estrogen receptor–positive breast cancer. FASEB J. 32, 588–600 (2018). www.fasebj.org" @default.
• W2756765053 created "2017-10-06" @default.
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• W2756765053 date "2018-01-04" @default.
• W2756765053 modified "2023-10-15" @default.
• W2756765053 title "miR‐125a‐3p inhibits ERα transactivation and overrides tamoxifen resistance by targeting CDK3 in estrogen receptor–positive breast cancer" @default.
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• W2756765053 doi "https://doi.org/10.1096/fj.201700461rr" @default.
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