Estrogen Regulation of microRNA Expression

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Estrogens have a wide variety of physiological functions as sex steroid hormones in women and in men. Estrogens have apparent anti-aging properties in brain, cardiovascular tissues, and bone. Estrogens regulate genes directly through binding to estrogen receptors alpha and beta (ERα and ERβ) that are ligand-activated transcription factors and indirectly by activating plasma membrane-associated ER which, in turns, activates intracellular signaling cascades leading to altered gene expression. Estrogens may also impact cellular signaling by binding to GPR30/GPER. MicroRNAs (miRNAs) are short (19-25 nucleotides), naturally-occurring, non-coding RNA molecules that base-pair with the 3’ untranslated region of target mRNAs. This interaction either blocks translation of the mRNA or targets the mRNA transcript to be degraded. The human genome contains ~2,578 miRNAs. Aberrant patterns of miRNA expression are implicated in human diseases including estrogen-related diseases including breast cancer. miRNAs regulated by estrogens have been identified Zebrafish, mouse tissues, and in human cells and tissues including breast and myometrial tumors. The mechanism for estrogen regulation of miRNA expression and the role of estrogen-regulated miRNAs in normal homeostasis, reproduction, lactation, and in cancer is only beginning to be explored.