MicroRNA-320a sensitizes tamoxifen-resistant breast cancer cells to tamoxifen by targeting ARPP-19 and ERRγ

Sci Rep. 2015 Mar 4;5:8735. doi: 10.1038/srep08735.


Tamoxifen represents a major adjuvant therapy to those patients with estrogen receptor-alpha positive breast cancer. However, tamoxifen resistance occurs quite often, either de novo or acquired during treatment. To investigate the role of miR-320a in the development of resistance to tamoxifen, we established tamoxifen-resistant (TamR) models by continually exposing MCF-7 or T47D breast cancer cells to tamoxifen, and identified microRNA(miRNA)-320a as a down-regulated miRNA in tamoxifen resistant cells. Re-expression of miR-320a was sufficient to sensitize TamR cells to tamoxifen by targeting cAMP-regulated phosphoprotein (ARPP-19) and estrogen-related receptor gamma (ERRγ) as well as their downstream effectors, c-Myc and Cyclin D1. Furthermore, progesterone (P4) promoted the expression of miR-320a by repressing c-Myc expression, while estrogen (E2) exerted the opposite effect. These results suggest the potential therapeutic approach for tamoxifen-resistant breast cancer by restorating miR-320a expression or depleting ARPP-19/ERRγ expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Hormonal / pharmacology
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Drug Resistance, Neoplasm / genetics*
  • Estrogens / pharmacology
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Knockdown Techniques
  • Humans
  • MCF-7 Cells
  • Mice, Nude
  • MicroRNAs / genetics*
  • Phosphoproteins / genetics*
  • Phosphoproteins / metabolism
  • Progesterone / pharmacology
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism
  • Receptors, Estrogen / genetics*
  • Receptors, Estrogen / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tamoxifen / pharmacology*
  • Xenograft Model Antitumor Assays / methods


  • Antineoplastic Agents, Hormonal
  • ESRRG protein, human
  • Estrogens
  • MIRN320 microRNA, human
  • MicroRNAs
  • Phosphoproteins
  • Proto-Oncogene Proteins c-myc
  • Receptors, Estrogen
  • cyclic AMP-regulated phosphoprotein 19
  • Tamoxifen
  • Progesterone