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

Oncogene. 2015 Jul 23;34(30):3895-907. doi: 10.1038/onc.2014.430. Epub 2014 Dec 22.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Hormonal / pharmacology*
  • Base Sequence
  • Binding Sites
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / genetics
  • Cell Proliferation
  • Cyclin-Dependent Kinase 3 / genetics*
  • Cyclin-Dependent Kinase 3 / metabolism
  • Drug Resistance, Neoplasm
  • Estrogen Receptor alpha / physiology*
  • Female
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MCF-7 Cells
  • Mice, Nude
  • MicroRNAs / physiology*
  • Phosphorylation
  • Protein Processing, Post-Translational
  • RNA Interference
  • Tamoxifen / pharmacology*
  • Transcriptional Activation
  • Xenograft Model Antitumor Assays


  • Antineoplastic Agents, Hormonal
  • ESR1 protein, human
  • Estrogen Receptor alpha
  • MIRN873 microRNA, human
  • MicroRNAs
  • Tamoxifen
  • CDK3 protein, human
  • Cyclin-Dependent Kinase 3