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Regulation of Krüppel-Like Factor 4 (KLF4) expression through the transcription factor Yin-Yang 1 (YY1) in non-Hodgkin B-cell lymphoma

Krüppel-Like Factor 4 (KLF4) is a member of the KLF transcription factor family, and evidence suggests that KLF4 is either an oncogene or a tumor suppressor. The regulatory mechanism underlying KLF4 expression in cancer, and specifically in lymphoma, is still not understood. Bioinformatics analysis...

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Autores principales: Morales-Martinez, Mario, Valencia-Hipolito, Alberto, Vega, Gabriel G., Neri, Natividad, Nambo, Maria J., Alvarado, Isabel, Cuadra, Ivonne, Duran-Padilla, Marco A., Martinez-Maza, Otoniel, Huerta-Yepez, Sara, Vega, Mario I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6481341/
https://www.ncbi.nlm.nih.gov/pubmed/31040909
http://dx.doi.org/10.18632/oncotarget.26745
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author Morales-Martinez, Mario
Valencia-Hipolito, Alberto
Vega, Gabriel G.
Neri, Natividad
Nambo, Maria J.
Alvarado, Isabel
Cuadra, Ivonne
Duran-Padilla, Marco A.
Martinez-Maza, Otoniel
Huerta-Yepez, Sara
Vega, Mario I.
author_facet Morales-Martinez, Mario
Valencia-Hipolito, Alberto
Vega, Gabriel G.
Neri, Natividad
Nambo, Maria J.
Alvarado, Isabel
Cuadra, Ivonne
Duran-Padilla, Marco A.
Martinez-Maza, Otoniel
Huerta-Yepez, Sara
Vega, Mario I.
author_sort Morales-Martinez, Mario
collection PubMed
description Krüppel-Like Factor 4 (KLF4) is a member of the KLF transcription factor family, and evidence suggests that KLF4 is either an oncogene or a tumor suppressor. The regulatory mechanism underlying KLF4 expression in cancer, and specifically in lymphoma, is still not understood. Bioinformatics analysis revealed two YY1 putative binding sites in the KLF4 promoter region (-950 bp and -105 bp). Here, the potential regulation of KLF4 by YY1 in NHL was analyzed. Mutation of the putative YY1 binding sites in a previously reported system containing the KLF4 promoter region and CHIP analysis confirmed that these binding sites are important for KLF4 regulation. B-NHL cell lines showed that both KLF4 and YY1 are co-expressed, and transfection with siRNA-YY1 resulted in significant inhibition of KLF4. The clinical implications of YY1 in the transcriptional regulation of KLF4 were investigated by IHC in a TMA with 43 samples of subtypes DLBCL and FL, and all tumor tissues expressing YY1 demonstrated a correlation with KLF4 expression, which was consistent with bioinformatics analyses in several databases. Our findings demonstrated that KLF4 can be transcriptionally regulated by YY1 in B-NHL, and a correlation between YY1 expression and KLF4 was found in clinical samples. Hence, both YY1 and KLF4 may be possible therapeutic biomarkers of NHL.
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spelling pubmed-64813412019-04-30 Regulation of Krüppel-Like Factor 4 (KLF4) expression through the transcription factor Yin-Yang 1 (YY1) in non-Hodgkin B-cell lymphoma Morales-Martinez, Mario Valencia-Hipolito, Alberto Vega, Gabriel G. Neri, Natividad Nambo, Maria J. Alvarado, Isabel Cuadra, Ivonne Duran-Padilla, Marco A. Martinez-Maza, Otoniel Huerta-Yepez, Sara Vega, Mario I. Oncotarget Research Paper Krüppel-Like Factor 4 (KLF4) is a member of the KLF transcription factor family, and evidence suggests that KLF4 is either an oncogene or a tumor suppressor. The regulatory mechanism underlying KLF4 expression in cancer, and specifically in lymphoma, is still not understood. Bioinformatics analysis revealed two YY1 putative binding sites in the KLF4 promoter region (-950 bp and -105 bp). Here, the potential regulation of KLF4 by YY1 in NHL was analyzed. Mutation of the putative YY1 binding sites in a previously reported system containing the KLF4 promoter region and CHIP analysis confirmed that these binding sites are important for KLF4 regulation. B-NHL cell lines showed that both KLF4 and YY1 are co-expressed, and transfection with siRNA-YY1 resulted in significant inhibition of KLF4. The clinical implications of YY1 in the transcriptional regulation of KLF4 were investigated by IHC in a TMA with 43 samples of subtypes DLBCL and FL, and all tumor tissues expressing YY1 demonstrated a correlation with KLF4 expression, which was consistent with bioinformatics analyses in several databases. Our findings demonstrated that KLF4 can be transcriptionally regulated by YY1 in B-NHL, and a correlation between YY1 expression and KLF4 was found in clinical samples. Hence, both YY1 and KLF4 may be possible therapeutic biomarkers of NHL. Impact Journals LLC 2019-03-15 /pmc/articles/PMC6481341/ /pubmed/31040909 http://dx.doi.org/10.18632/oncotarget.26745 Text en Copyright: © 2019 Morales-Martinez et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (http://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Morales-Martinez, Mario
Valencia-Hipolito, Alberto
Vega, Gabriel G.
Neri, Natividad
Nambo, Maria J.
Alvarado, Isabel
Cuadra, Ivonne
Duran-Padilla, Marco A.
Martinez-Maza, Otoniel
Huerta-Yepez, Sara
Vega, Mario I.
Regulation of Krüppel-Like Factor 4 (KLF4) expression through the transcription factor Yin-Yang 1 (YY1) in non-Hodgkin B-cell lymphoma
title Regulation of Krüppel-Like Factor 4 (KLF4) expression through the transcription factor Yin-Yang 1 (YY1) in non-Hodgkin B-cell lymphoma
title_full Regulation of Krüppel-Like Factor 4 (KLF4) expression through the transcription factor Yin-Yang 1 (YY1) in non-Hodgkin B-cell lymphoma
title_fullStr Regulation of Krüppel-Like Factor 4 (KLF4) expression through the transcription factor Yin-Yang 1 (YY1) in non-Hodgkin B-cell lymphoma
title_full_unstemmed Regulation of Krüppel-Like Factor 4 (KLF4) expression through the transcription factor Yin-Yang 1 (YY1) in non-Hodgkin B-cell lymphoma
title_short Regulation of Krüppel-Like Factor 4 (KLF4) expression through the transcription factor Yin-Yang 1 (YY1) in non-Hodgkin B-cell lymphoma
title_sort regulation of krüppel-like factor 4 (klf4) expression through the transcription factor yin-yang 1 (yy1) in non-hodgkin b-cell lymphoma
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6481341/
https://www.ncbi.nlm.nih.gov/pubmed/31040909
http://dx.doi.org/10.18632/oncotarget.26745
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