NF-κB Mediates the Expression of TBX15 in Cancer Cells

TBX15 is a T-box transcription factor essential for development, also proposed as a marker in prostate cancer; and, recently, its antiapoptotic function indicates a role in carcinogenesis. Regulation of TBX15 is uncovered. In this study, we investigated the regulation of TBX15 expression in human ca...

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Autores principales: Arribas, Jéssica, Cajuso, Tatiana, Rodio, Angela, Marcos, Ricard, Leonardi, Antonio, Velázquez, Antonia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4915632/
https://www.ncbi.nlm.nih.gov/pubmed/27327083
http://dx.doi.org/10.1371/journal.pone.0157761
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author Arribas, Jéssica
Cajuso, Tatiana
Rodio, Angela
Marcos, Ricard
Leonardi, Antonio
Velázquez, Antonia
author_facet Arribas, Jéssica
Cajuso, Tatiana
Rodio, Angela
Marcos, Ricard
Leonardi, Antonio
Velázquez, Antonia
author_sort Arribas, Jéssica
collection PubMed
description TBX15 is a T-box transcription factor essential for development, also proposed as a marker in prostate cancer; and, recently, its antiapoptotic function indicates a role in carcinogenesis. Regulation of TBX15 is uncovered. In this study, we investigated the regulation of TBX15 expression in human cancer cells, by analyzing the regulatory function of a 5’-distal conserved region of TBX15. Bisulfite sequencing showed high methylation of the CpG island contained in this region that was not correlated with TBX15 mRNA levels, in the cancer cell lines analyzed; however, after 5-aza-dC treatment of TPC-1 cells an increase of TBX15 expression was observed. We also found a significant response of TBX15 to TNF-α activation of the NF-κB pathway using five cancer cell lines, and similar results were obtained when NF-κB was activated with PMA/ionomycin. Next, by luciferase reporter assays, we identified the TBX15 regulatory region containing two functional NF-κB binding sites with response to NF-κBp65, mapping on the -3302 and -3059 positions of the TBX15 gene. Moreover, a direct interaction of NF-κBp65 with one of the two NF-κB binding sites was indicated by ChIP assays. In summary, we provide novel data showing that NF-κB signaling up-regulates TBX15 expression in cancer cells. Furthermore, the link between TBX15 and NF-κB found in this study may be important to understand cancer and development processes.
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spelling pubmed-49156322016-07-06 NF-κB Mediates the Expression of TBX15 in Cancer Cells Arribas, Jéssica Cajuso, Tatiana Rodio, Angela Marcos, Ricard Leonardi, Antonio Velázquez, Antonia PLoS One Research Article TBX15 is a T-box transcription factor essential for development, also proposed as a marker in prostate cancer; and, recently, its antiapoptotic function indicates a role in carcinogenesis. Regulation of TBX15 is uncovered. In this study, we investigated the regulation of TBX15 expression in human cancer cells, by analyzing the regulatory function of a 5’-distal conserved region of TBX15. Bisulfite sequencing showed high methylation of the CpG island contained in this region that was not correlated with TBX15 mRNA levels, in the cancer cell lines analyzed; however, after 5-aza-dC treatment of TPC-1 cells an increase of TBX15 expression was observed. We also found a significant response of TBX15 to TNF-α activation of the NF-κB pathway using five cancer cell lines, and similar results were obtained when NF-κB was activated with PMA/ionomycin. Next, by luciferase reporter assays, we identified the TBX15 regulatory region containing two functional NF-κB binding sites with response to NF-κBp65, mapping on the -3302 and -3059 positions of the TBX15 gene. Moreover, a direct interaction of NF-κBp65 with one of the two NF-κB binding sites was indicated by ChIP assays. In summary, we provide novel data showing that NF-κB signaling up-regulates TBX15 expression in cancer cells. Furthermore, the link between TBX15 and NF-κB found in this study may be important to understand cancer and development processes. Public Library of Science 2016-06-21 /pmc/articles/PMC4915632/ /pubmed/27327083 http://dx.doi.org/10.1371/journal.pone.0157761 Text en © 2016 Arribas 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
Arribas, Jéssica
Cajuso, Tatiana
Rodio, Angela
Marcos, Ricard
Leonardi, Antonio
Velázquez, Antonia
NF-κB Mediates the Expression of TBX15 in Cancer Cells
title NF-κB Mediates the Expression of TBX15 in Cancer Cells
title_full NF-κB Mediates the Expression of TBX15 in Cancer Cells
title_fullStr NF-κB Mediates the Expression of TBX15 in Cancer Cells
title_full_unstemmed NF-κB Mediates the Expression of TBX15 in Cancer Cells
title_short NF-κB Mediates the Expression of TBX15 in Cancer Cells
title_sort nf-κb mediates the expression of tbx15 in cancer cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4915632/
https://www.ncbi.nlm.nih.gov/pubmed/27327083
http://dx.doi.org/10.1371/journal.pone.0157761
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