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MiR-873 regulates ERα transcriptional activity and tamoxifen resistance via targeting CDK3 in breast cancer cells

Oncogene volume 34, pages 3895–3907 (2015)Cite this article

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A Corrigendum to this article was published on 23 July 2015

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Abstract

miRNAs (microRNAs) are frequently and 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 tumor 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.

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  • 23 July 2015

    This article has been corrected since Advance Online Publication and a corrigendum is also printed in this issue.

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Acknowledgements

We are grateful to Mingjun Bi, Anne-Marie Overstreet and Alex Meredith for their advice, discussion and editorial assistance. We thank Dr. Guanxuan Tan and his lab members for reagents and advice. We also thank Bill Evans for editorial support and for improving the English. This study was supported by the National Natural Science Foundation of China (Grant Nos. 81102005 and 31271154) and the National High Technology Research and Development Programme of China (Grant No. 2014AA020516).

Author information

Author notes

  1. Dr X Yang, Department of Cancer and Cell Biology, University of Cincinnati College of Medicine, 3125 Eden Avenue, Cincinnati, OH 45267, USAE-mail: Stanleyxingyuan@hotmail.com

  2. Dr C Zhang, Institute of Disease Control and Prevention, Chinese Academy of Military Medical Sciences, 20 Dongdajie, Fengtai District, Beijing 100071, China. E-mail: zhangcfu@gmail.com

Authors and Affiliations

  1. Institute of Disease Control and Prevention, Chinese Academy of Military Medical Sciences, Beijing, China

    J Cui, Z Lu, R Wu, Y Sun, H Song & C Zhang

  2. Beijing Institute for Neuroscience, Capital Medical University, Beijing, China

    Y Yang

  3. Department of Molecular & Biomedical Pharmacology, University of Kentucky College of Medicine, Lexington, KY, USA

    H Li

  4. The Affiliated Hospital of Jiujiang University, Jiujiang, China

    Y Leng & K Qian

  5. Department of Animal Sciences and Technology, Jilin Agriculture University, Changchun, China

    Q Huang

  6. Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA

    C Zhang

  7. Urology Department, the First Hospital of Nanchang University, Nanchang, China

    J Chen & T Sun

  8. Department of Applied Chemistry, College of Chemistry & Molecular Engineering, Peking University, Beijing, China

    X Wei

  9. Department of Chemistry, College of Arts and Sciences, Indiana University-Purdue University Fort Wayne Fort Wayne, IN, USA

    P Jing

  10. Institute of Health Sciences, Anhui University, Hefei, China

    X Yang

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Cui, J., Yang, Y., Li, H. et al. MiR-873 regulates ERα transcriptional activity and tamoxifen resistance via targeting CDK3 in breast cancer cells. Oncogene 34, 3895–3907 (2015). https://doi.org/10.1038/onc.2014.430

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