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microRNAs 424 and 503 are mediators of the anti-proliferative and anti-invasive action of the thyroid hormone receptor beta

AuthorsRuiz-Llorente, Lidia ; Ardila-González, Soraya; Fanjul, Luisa F.; Martínez-Iglesias, Olaia ; Aranda, Ana
Thyroid hormone receptor
Issue Date2014
PublisherImpact Journals
CitationOncotarget 5(10): 2918-2933 (2014)
AbstractThe thyroid hormone receptors (TRs) mediate tumor suppressive effects in hepatocarcinoma and breast cancer cells. Here we show that incubation of hepatocarcinoma SK-hep1 cells expressing TRb with the thyroid hormone T3 induces transcription of the polycistronic message coding for microRNAs 424 and 503. TRb binds to the promoter region of these miRNAs and T3 induces an exchange of corepressors and coactivators inducing histone acetylation and transcriptional stimulation. We have validated cell cycle components as targets of these miRNAs. Overexpression of miR-424 mimicked the repressive effect of T3 on cell proliferation, growth in suspension, migration and invasion. Knockdown of miR-424 or miR-503 reduced the inhibitory effect of the hormone. T3 increased miR-424 and miR-503 in breast cancer cells expressing TRb, and this induction is also involved in the anti-invasive effects of the hormone. Furthermore, miR-424 or miR-503 depletion enhanced extravasation to the lungs of hepatocarcinoma cells injected in the tail vein of mice. The levels of these miRNAs were reduced in xenograft tumors formed in hypothyroid nude mice that are more invasive. Therefore, miR-424 or miR-503 mediate anti-proliferative and anti-invasive actions of TRb both in cultured cells and in vivo. © 2008-2014 Impact Journals, LLC.
DescriptionLicensed under a Creative Commons Attribution 3.0 License.
Publisher version (URL)http://dx.doi.org/10.18632/oncotarget.1577
Identifierse-issn: 1949-2553
Appears in Collections:(IIBM) Artículos
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