miRNAs regulated by estrogens, tamoxifen, and endocrine disruptors and their downstream gene targets

Mol Cell Endocrinol. 2015 Dec 15;418 Pt 3(0 3):273-97. doi: 10.1016/j.mce.2015.01.035. Epub 2015 Feb 3.

Abstract

MicroRNAs (miRNAs) are short (22 nucleotides), single-stranded, non-coding RNAs that form complimentary base-pairs with the 3' untranslated region of target mRNAs within the RNA-induced silencing complex (RISC) and block translation and/or stimulate mRNA transcript degradation. The non-coding miRBase (release 21, June 2014) reports that human genome contains ∼ 2588 mature miRNAs which regulate ∼ 60% of human protein-coding mRNAs. Dysregulation of miRNA expression has been implicated in estrogen-related diseases including breast cancer and endometrial cancer. The mechanism for estrogen regulation of miRNA expression and the role of estrogen-regulated miRNAs in normal homeostasis, reproduction, lactation, and in cancer is an area of great research and clinical interest. Estrogens regulate miRNA transcription through estrogen receptors α and β in a tissue-specific and cell-dependent manner. This review focuses primarily on the regulation of miRNA expression by ligand-activated ERs and their bona fide gene targets and includes miRNA regulation by tamoxifen and endocrine disrupting chemicals (EDCs) in breast cancer and cell lines.

Keywords: Dicer; Drosha; Endocrine disrupting chemical; Endocrine-resistance; Estrogen; Estrogen receptor; Tamoxifen; Transcription; mRNA stability; miRNA.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Cell Line, Tumor
  • Estrogen Receptor alpha / genetics
  • Estrogen Receptor beta / genetics
  • Estrogens / pharmacology*
  • Estrogens / therapeutic use
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • MicroRNAs / genetics*
  • Tamoxifen / pharmacology*
  • Tamoxifen / therapeutic use

Substances

  • ESR1 protein, human
  • ESR2 protein, human
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Estrogens
  • MicroRNAs
  • Tamoxifen