Author(s)

J. Cui, Department of Cancer and Cell Biology, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Institute of Disease Control and Prevention, Chinese Academy of Military Medical Sciences, Beijing, China;
M. Bi, Department of Cancer and Cell Biology, University of Cincinnati College of Medicine, Cincinnati, OH, USA
A. Overstreet, Department of Cancer and Cell Biology, University of Cincinnati College of Medicine, Cincinnati, OH, USA
Y. Yang, Department of Neurobiology, Beijing Institute for Neuroscience, Capital Medical University, Beijing, China
H. Li, 4 Department of Molecular and Biomedical Pharmacology, University of Kentucky College of Medicine, Lexington, KY, USA
Y. Leng, 5 Department of Pathology, The Affiliated Hospital of Jiujiang University, Jiujiang, China
K. Qian, 5 Department of Pathology, The Affiliated Hospital of Jiujiang University, Jiujiang, China
Q. Huang, Department of Animal Sciences and Technology, Jilin Agriculture University, Changchun, China
C. Zhang, 7 Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA
Z. Lu, Institute of Disease Control and Prevention, Chinese Academy of Military Medical Sciences, Beijing, China;
J. Chen, Urology Department, The First Hospital of Nanchang University, Nanchang, China
R. Wu, Institute of Disease Control and Prevention, Chinese Academy of Military Medical Sciences, Beijing, China;
Y. Sun, Institute of Disease Control and Prevention, Chinese Academy of Military Medical Sciences, Beijing, China;
H. Hong, Institute of Disease Control and Prevention, Chinese Academy of Military Medical Sciences, Beijing, China;
X. Wei, Department of Applied Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing, China
Peng Jing, Department of Chemistry, College of Arts and Sciences, Indiana University-Purdue University Fort Wayne, Fort Wayne, IN, USAFollow
A. Meredith, Department of Cancer and Cell Biology, University of Cincinnati College of Medicine, Cincinnati, OH, USA
X. Yang, Department of Cancer and Cell Biology, University of Cincinnati College of Medicine, Cincinnati, OH, USA
C. Zhang, Institute of Disease Control and Prevention, Chinese Academy of Military Medical Sciences, Beijing, China;

Document Type

Article

Publication Date

Fall 12-22-2014

Publication Source

Oncogene

Inclusive pages

1-13

DOI

10.1038/onc.2014.430

Publisher

Nature Publishing Group

Place of Publication

London, UK

Peer Reviewed

yes

Abstract

MiRNAs (microRNAs) are frequently aberrantly expressed in many cancers. MiR-873 has been revealed to be downregulated in colorectal cancer and glioblastoma. However, its function remains unclear. Here, we report that miR-873 is downregulated in breast cancer compared with normal tissue. Enforced expression of miR-873 decreases the transcriptional activity of ER (estrogen receptor) α but not ERβ through the modulation of ERα phosphorylation in ER positive breast cancer cells. We also found that MiR-873 inhibits breast cancer cell proliferation and tumor growth in nude mice. Reporter gene assays revealed cyclin-dependent kinase 3 (CDK3) as a direct target of miR-873. CDK3 was shown to be overexpressed in breast cancer and phosphorylate ERα at Ser104/116 and Ser118. Furthermore, we found that Mir-873 inhibits ER activity and cell growth via targeting CDK3. Interestingly, miR-873 was observed to be downregulated in tamoxifen resistant MCF-7/TamR cells, while CDK3 is overexpressed in these cells. More importantly, re-expression of miR-873 reversed tamoxifen resistance in MCF-7/TamR cells. Our data demonstrate that miR-873 is a novel tumor suppressor in ER positive breast cancer and a potential therapeutic approach for treatment of tamoxifen resistant breast cancer.

Disciplines

Biological Phenomena, Cell Phenomena, and Immunity | Chemistry

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