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MiRNAs and estrogen action.

ABSTRACT: MicroRNAs (miRNAs) are short, noncoding RNAs that generally base-pair within the 3' untranslated region of target mRNAs causing translational inhibition and/or mRNA degradation. Estradiol (E(2)) and other estrogen receptor (ER) ligands suppress or stimulate miRNA expression in human breast cancer cells, endometrial cells, rat mammary gland, and mouse uterus, and post-translationally regulate protein expression. Aberrant miRNA expression is implicated in estrogen-related breast and endometrial cancers, and several miRNAs downregulate ER?. The role of estrogen-regulated miRNA expression, the target genes of these miRNAs, and the role of miRNAs in health and disease is a 'hot' area of research that will yield new insight into molecular mechanisms of estrogen action.

SUBMITTER: Klinge CM

PROVIDER: S-EPMC3348384 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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miRNAs and estrogen action.

Klinge Carolyn M CM

Trends in endocrinology and metabolism: TEM 20120411 5

MicroRNAs (miRNAs) are short, noncoding RNAs that generally base-pair within the 3' untranslated region of target mRNAs causing translational inhibition and/or mRNA degradation. Estradiol (E(2)) and other estrogen receptor (ER) ligands suppress or stimulate miRNA expression in human breast cancer cells, endometrial cells, rat mammary gland, and mouse uterus, and post-translationally regulate protein expression. Aberrant miRNA expression is implicated in estrogen-related breast and endometrial ca ...[more]

PMID: 22503553

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Project description:Autophagy, or cellular self-digestion, is an essential cellular process imperative for energy homeostasis, development, differentiation, and survival. However, the intrinsic factors that bring about the sex-biased differences in liver autophagy are still unknown. In this work, we found that autophagic genes variably expresses in the steroidogenic tissues, mostly abundant in liver, and is influenced by the individual's sexuality. Starvation-induced autophagy in a time-dependent female-dominated manner, and upon starvation, a strong gender responsive circulating steroid-HK2 relation was observed, which highlighted the importance of estrogen in autophagy regulation. This was further confirmed by the enhanced or suppressed autophagy upon estrogen addition (male) or blockage (female), respectively. In addition, we found that estrogen proved to be the common denominator between stress management, glucose metabolism, and autophagic action in female fish. To understand further, we used estrogen receptor (ER)α- and ER-β2-knockout (KO) medaka and found ER-specific differences in sex-biased autophagy. Interestingly, starvation resulted in significantly elevated mTOR transcription (compared with control) in male ERα-KO fish while HK2 and ULK activation was greatly decreased in both KO fish in a female oriented fashion. Later, ChIP analysis confirmed that, NRF2, an upstream regulator of mTOR, only binds to ERα, while both ERα and ERβ2 are effectively pulled down the HK2 and LC3. FIHC data show that, in both ER-KO fish, LC3 nuclear-cytoplasmic transport and its associated pathways involving SIRT1 and DOR were greatly affected. Cumulatively, our data suggest that, ERα-KO strongly affected the early autophagic initiation and altered the LC3 nuclear-cytoplasmic translocation, thereby influencing the sex-biased final autophagosome formation in medaka. Thus, existence of steroid responsive autophagy regulatory-switches and sex-biased steroid/steroid receptor availability influences the gender-skewed autophagy. Expectedly, this study may furnish newer appreciation for gender-specific medicine research and therapeutics.

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MiRNAs and estrogen action.

Publications

miRNAs and estrogen action.

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