Abstract
MicroRNAs (miRs) are small non-coding RNAs aberrantly expressed in human tumors. Increasing evidence suggests that miRNAs are functionally important in cancers. We demonstrated miR-204 exerts its function by targeting gene involved in tumor growth and chemotherapy drugs reactivity. Here, we show that Trichostatin A (TSA) could increase ERα expression in MCF-7 and MDA-MB-231 cells by reducing miR204. Analysis of tumors growth inhibition shows that TSA promotes ERα expression, which could be reversed by miR-204 mimic transfection. When miR-204 is down regulated, the inhibition of TAM on breast cancer cells is enhanced. Caspase 3 activity is also increased. TSA and TAM combination inhibits Mcl-1 expression by decreasing phosphorylation of AKT induced by ERα increase in vivo and in vitro.
Keywords:
Breast cancer; Cell inhibition; Estrogen receptors (ER); miR-204.
Copyright © 2015 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / genetics*
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Adenocarcinoma / metabolism
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Adenocarcinoma / pathology
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Animals
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Antineoplastic Agents, Hormonal / pharmacology
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Breast Neoplasms / genetics*
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Breast Neoplasms / metabolism
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Breast Neoplasms / pathology
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Cell Line
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Cell Proliferation / drug effects
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Estrogen Receptor alpha / genetics*
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Estrogen Receptor alpha / metabolism
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Female
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Gene Expression Regulation, Neoplastic*
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Humans
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Hydroxamic Acids / pharmacology
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MCF-7 Cells
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Mice, Nude
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MicroRNAs / genetics
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MicroRNAs / metabolism*
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Protein Synthesis Inhibitors / pharmacology
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Proto-Oncogene Proteins c-akt / genetics*
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Proto-Oncogene Proteins c-akt / metabolism
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Signal Transduction
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TOR Serine-Threonine Kinases / genetics*
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TOR Serine-Threonine Kinases / metabolism
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Tamoxifen / pharmacology
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Tumor Burden / drug effects
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Xenograft Model Antitumor Assays
Substances
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Antineoplastic Agents, Hormonal
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ESR1 protein, human
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Estrogen Receptor alpha
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Hydroxamic Acids
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MIRN204 microRNA, human
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MicroRNAs
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Protein Synthesis Inhibitors
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Tamoxifen
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trichostatin A
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MTOR protein, human
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Proto-Oncogene Proteins c-akt
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TOR Serine-Threonine Kinases