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miR‐125a‐3p inhibits ERα transactivation and overrides tamoxifen resistance by targeting CDK3 in estrogen receptor–positive breast cancer
Author(s) -
Zheng Lufeng,
Meng Xia,
Li Xiaoman,
Zhang Yan,
Li Cheng,
Xiang Chenxi,
Xing Yingying,
Xia Yufeng,
Xi Tao
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201700461rr
Subject(s) - tamoxifen , breast cancer , transactivation , estrogen receptor , cancer research , cancer , cell growth , cyclin d1 , biology , medicine , cell cycle , gene expression , biochemistry , gene , genetics
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 G 1 /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