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

•Reviews miRNA biogenesis and regulation by estradiol•Summarizes miRNA regulation by tamoxifen and other ER ligands•Reviews regulation of miRNAs by endocrine disrupting chemicals

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.