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RNA-Binding Protein FXR1 Regulates p21 and TERC RNA to Bypass p53-Mediated Cellular Senescence in OSCC

RNA-binding proteins (RBP) regulate numerous aspects of co- and post-transcriptional gene expression in cancer cells. Here, we demonstrate that RBP, fragile X-related protein 1 (FXR1), plays an essential role in cellular senescence by utilizing mRNA turnover pathway. We report that overexpressed FXR...

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Autores principales: Majumder, Mrinmoyee, House, Reniqua, Palanisamy, Nallasivam, Qie, Shuo, Day, Terrence A., Neskey, David, Diehl, J. Alan, Palanisamy, Viswanathan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015924/
https://www.ncbi.nlm.nih.gov/pubmed/27606879
http://dx.doi.org/10.1371/journal.pgen.1006306
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author Majumder, Mrinmoyee
House, Reniqua
Palanisamy, Nallasivam
Qie, Shuo
Day, Terrence A.
Neskey, David
Diehl, J. Alan
Palanisamy, Viswanathan
author_facet Majumder, Mrinmoyee
House, Reniqua
Palanisamy, Nallasivam
Qie, Shuo
Day, Terrence A.
Neskey, David
Diehl, J. Alan
Palanisamy, Viswanathan
author_sort Majumder, Mrinmoyee
collection PubMed
description RNA-binding proteins (RBP) regulate numerous aspects of co- and post-transcriptional gene expression in cancer cells. Here, we demonstrate that RBP, fragile X-related protein 1 (FXR1), plays an essential role in cellular senescence by utilizing mRNA turnover pathway. We report that overexpressed FXR1 in head and neck squamous cell carcinoma targets (G-quadruplex (G4) RNA structure within) both mRNA encoding p21 (Cyclin-Dependent Kinase Inhibitor 1A (CDKN1A, Cip1) and the non-coding RNA Telomerase RNA Component (TERC), and regulates their turnover to avoid senescence. Silencing of FXR1 in cancer cells triggers the activation of Cyclin-Dependent Kinase Inhibitors, p53, increases DNA damage, and ultimately, cellular senescence. Overexpressed FXR1 binds and destabilizes p21 mRNA, subsequently reduces p21 protein expression in oral cancer cells. In addition, FXR1 also binds and stabilizes TERC RNA and suppresses the cellular senescence possibly through telomerase activity. Finally, we report that FXR1-regulated senescence is irreversible and FXR1-depleted cells fail to form colonies to re-enter cellular proliferation. Collectively, FXR1 displays a novel mechanism of controlling the expression of p21 through p53-dependent manner to bypass cellular senescence in oral cancer cells.
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spelling pubmed-50159242016-09-27 RNA-Binding Protein FXR1 Regulates p21 and TERC RNA to Bypass p53-Mediated Cellular Senescence in OSCC Majumder, Mrinmoyee House, Reniqua Palanisamy, Nallasivam Qie, Shuo Day, Terrence A. Neskey, David Diehl, J. Alan Palanisamy, Viswanathan PLoS Genet Research Article RNA-binding proteins (RBP) regulate numerous aspects of co- and post-transcriptional gene expression in cancer cells. Here, we demonstrate that RBP, fragile X-related protein 1 (FXR1), plays an essential role in cellular senescence by utilizing mRNA turnover pathway. We report that overexpressed FXR1 in head and neck squamous cell carcinoma targets (G-quadruplex (G4) RNA structure within) both mRNA encoding p21 (Cyclin-Dependent Kinase Inhibitor 1A (CDKN1A, Cip1) and the non-coding RNA Telomerase RNA Component (TERC), and regulates their turnover to avoid senescence. Silencing of FXR1 in cancer cells triggers the activation of Cyclin-Dependent Kinase Inhibitors, p53, increases DNA damage, and ultimately, cellular senescence. Overexpressed FXR1 binds and destabilizes p21 mRNA, subsequently reduces p21 protein expression in oral cancer cells. In addition, FXR1 also binds and stabilizes TERC RNA and suppresses the cellular senescence possibly through telomerase activity. Finally, we report that FXR1-regulated senescence is irreversible and FXR1-depleted cells fail to form colonies to re-enter cellular proliferation. Collectively, FXR1 displays a novel mechanism of controlling the expression of p21 through p53-dependent manner to bypass cellular senescence in oral cancer cells. Public Library of Science 2016-09-08 /pmc/articles/PMC5015924/ /pubmed/27606879 http://dx.doi.org/10.1371/journal.pgen.1006306 Text en © 2016 Majumder et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Majumder, Mrinmoyee
House, Reniqua
Palanisamy, Nallasivam
Qie, Shuo
Day, Terrence A.
Neskey, David
Diehl, J. Alan
Palanisamy, Viswanathan
RNA-Binding Protein FXR1 Regulates p21 and TERC RNA to Bypass p53-Mediated Cellular Senescence in OSCC
title RNA-Binding Protein FXR1 Regulates p21 and TERC RNA to Bypass p53-Mediated Cellular Senescence in OSCC
title_full RNA-Binding Protein FXR1 Regulates p21 and TERC RNA to Bypass p53-Mediated Cellular Senescence in OSCC
title_fullStr RNA-Binding Protein FXR1 Regulates p21 and TERC RNA to Bypass p53-Mediated Cellular Senescence in OSCC
title_full_unstemmed RNA-Binding Protein FXR1 Regulates p21 and TERC RNA to Bypass p53-Mediated Cellular Senescence in OSCC
title_short RNA-Binding Protein FXR1 Regulates p21 and TERC RNA to Bypass p53-Mediated Cellular Senescence in OSCC
title_sort rna-binding protein fxr1 regulates p21 and terc rna to bypass p53-mediated cellular senescence in oscc
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015924/
https://www.ncbi.nlm.nih.gov/pubmed/27606879
http://dx.doi.org/10.1371/journal.pgen.1006306
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