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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2015
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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. |
format | Online Article Text |
id | pubmed-4425007 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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