title: miRNAs regulated by estrogens, tamoxifen, and endocrine disruptors and their downstream gene targets.
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.
authors: Department of Biochemistry & Molecular Biology, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY 40292, USA. Electronic address: carolyn.klinge@louisville.edu.
authors: Carolyn M
authors: CM
authors: Klinge
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics*; D045744:Cell Line, Tumor; D047628:Estrogen Receptor alpha / Q000235:genetics; D047629:Estrogen Receptor beta / Q000235:genetics; D004967:Estrogens / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D013629:Tamoxifen / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: C506487:ESR1 protein, human; C000600034:ESR2 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D035683:MicroRNAs; D013629:Tamoxifen
keywords: Dicer; Drosha; Endocrine disrupting chemical; Endocrine-resistance; Estrogen; Estrogen receptor; Tamoxifen; Transcription; mRNA stability; miRNA