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

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.