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MicroRNA-16 Modulates HuR Regulation of Cyclin E1 in Breast Cancer Cells

RNA binding protein (RBPs) and microRNAs (miRNAs or miRs) are post-transcriptional regulators of gene expression that are implicated in development of cancers. Although their individual roles have been studied, the crosstalk between RBPs and miRNAs is under intense investigation. Here, we show that...

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Autores principales: Guo, Xun, Connick, Melanie C., Vanderhoof, Jennifer, Ishak, Mohammad-Ali, Hartley, Rebecca S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4425007/
https://www.ncbi.nlm.nih.gov/pubmed/25830480
http://dx.doi.org/10.3390/ijms16047112
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author Guo, Xun
Connick, Melanie C.
Vanderhoof, Jennifer
Ishak, Mohammad-Ali
Hartley, Rebecca S.
author_facet Guo, Xun
Connick, Melanie C.
Vanderhoof, Jennifer
Ishak, Mohammad-Ali
Hartley, Rebecca S.
author_sort Guo, Xun
collection PubMed
description RNA binding protein (RBPs) and microRNAs (miRNAs or miRs) are post-transcriptional regulators of gene expression that are implicated in development of cancers. Although their individual roles have been studied, the crosstalk between RBPs and miRNAs is under intense investigation. Here, we show that in breast cancer cells, cyclin E1 upregulation by the RBP HuR is through specific binding to regions in the cyclin E1 mRNA 3' untranslated region (3'UTR) containing U-rich elements. Similarly, miR-16 represses cyclin E1, dependent on its cognate binding sites in the cyclin E1 3'UTR. Evidence in the literature indicates that HuR can regulate miRNA expression and recruit or dissociate RNA-induced silencing complexes (RISC). Despite this, miR-16 and HuR do not affect the other’s expression level or binding to the cyclin E1 3'UTR. While HuR overexpression partially blocks miR-16 repression of a reporter mRNA containing the cyclin E1 3'UTR, it does not block miR-16 repression of endogenous cyclin E1 mRNA. In contrast, miR-16 blocks HuR-mediated upregulation of cyclin E1. Overall our results suggest that miR-16 can override HuR upregulation of cyclin E1 without affecting HuR expression or association with the cyclin E1 mRNA.
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spelling pubmed-44250072015-05-20 MicroRNA-16 Modulates HuR Regulation of Cyclin E1 in Breast Cancer Cells Guo, Xun Connick, Melanie C. Vanderhoof, Jennifer Ishak, Mohammad-Ali Hartley, Rebecca S. Int J Mol Sci Article RNA binding protein (RBPs) and microRNAs (miRNAs or miRs) are post-transcriptional regulators of gene expression that are implicated in development of cancers. Although their individual roles have been studied, the crosstalk between RBPs and miRNAs is under intense investigation. Here, we show that in breast cancer cells, cyclin E1 upregulation by the RBP HuR is through specific binding to regions in the cyclin E1 mRNA 3' untranslated region (3'UTR) containing U-rich elements. Similarly, miR-16 represses cyclin E1, dependent on its cognate binding sites in the cyclin E1 3'UTR. Evidence in the literature indicates that HuR can regulate miRNA expression and recruit or dissociate RNA-induced silencing complexes (RISC). Despite this, miR-16 and HuR do not affect the other’s expression level or binding to the cyclin E1 3'UTR. While HuR overexpression partially blocks miR-16 repression of a reporter mRNA containing the cyclin E1 3'UTR, it does not block miR-16 repression of endogenous cyclin E1 mRNA. In contrast, miR-16 blocks HuR-mediated upregulation of cyclin E1. Overall our results suggest that miR-16 can override HuR upregulation of cyclin E1 without affecting HuR expression or association with the cyclin E1 mRNA. MDPI 2015-03-30 /pmc/articles/PMC4425007/ /pubmed/25830480 http://dx.doi.org/10.3390/ijms16047112 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Guo, Xun
Connick, Melanie C.
Vanderhoof, Jennifer
Ishak, Mohammad-Ali
Hartley, Rebecca S.
MicroRNA-16 Modulates HuR Regulation of Cyclin E1 in Breast Cancer Cells
title MicroRNA-16 Modulates HuR Regulation of Cyclin E1 in Breast Cancer Cells
title_full MicroRNA-16 Modulates HuR Regulation of Cyclin E1 in Breast Cancer Cells
title_fullStr MicroRNA-16 Modulates HuR Regulation of Cyclin E1 in Breast Cancer Cells
title_full_unstemmed MicroRNA-16 Modulates HuR Regulation of Cyclin E1 in Breast Cancer Cells
title_short MicroRNA-16 Modulates HuR Regulation of Cyclin E1 in Breast Cancer Cells
title_sort microrna-16 modulates hur regulation of cyclin e1 in breast cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4425007/
https://www.ncbi.nlm.nih.gov/pubmed/25830480
http://dx.doi.org/10.3390/ijms16047112
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