Cargando…

Esophageal squamous cell carcinoma transcriptome reveals the effect of FOXM1 on patient outcome through novel PIK3R3 mediated activation of PI3K signaling pathway

Esophageal squamous cell carcinoma (ESCC) presents poor prognosis, and patients diagnosed with this tumor currently lack target treatments. Therefore, in order to identify potential targets for ESCC treatment, we carried out a transcriptome analysis with ESCC and paired nonmalignant surrounding muco...

Descripción completa

Detalles Bibliográficos
Autores principales: Nicolau-Neto, Pedro, Da Costa, Nathalia Meireles, de Souza Santos, Paulo Thiago, Gonzaga, Isabela Martins, Ferreira, Maria Aparecida, Guaraldi, Simone, Moreira, Miguel Angelo, Seuánez, Hector N., Brewer, Lilian, Bergmann, Anke, Boroni, Mariana, Mencalha, Andre Luiz, Kruel, Cleber Dario Pinto, Lima, Sheila Coelho Soares, Esposito, Dominic, Simão, Tatiana Almeida, Pinto, Luis Felipe Ribeiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5908275/
https://www.ncbi.nlm.nih.gov/pubmed/29682174
http://dx.doi.org/10.18632/oncotarget.24621
_version_ 1783315690898325504
author Nicolau-Neto, Pedro
Da Costa, Nathalia Meireles
de Souza Santos, Paulo Thiago
Gonzaga, Isabela Martins
Ferreira, Maria Aparecida
Guaraldi, Simone
Moreira, Miguel Angelo
Seuánez, Hector N.
Brewer, Lilian
Bergmann, Anke
Boroni, Mariana
Mencalha, Andre Luiz
Kruel, Cleber Dario Pinto
Lima, Sheila Coelho Soares
Esposito, Dominic
Simão, Tatiana Almeida
Pinto, Luis Felipe Ribeiro
author_facet Nicolau-Neto, Pedro
Da Costa, Nathalia Meireles
de Souza Santos, Paulo Thiago
Gonzaga, Isabela Martins
Ferreira, Maria Aparecida
Guaraldi, Simone
Moreira, Miguel Angelo
Seuánez, Hector N.
Brewer, Lilian
Bergmann, Anke
Boroni, Mariana
Mencalha, Andre Luiz
Kruel, Cleber Dario Pinto
Lima, Sheila Coelho Soares
Esposito, Dominic
Simão, Tatiana Almeida
Pinto, Luis Felipe Ribeiro
author_sort Nicolau-Neto, Pedro
collection PubMed
description Esophageal squamous cell carcinoma (ESCC) presents poor prognosis, and patients diagnosed with this tumor currently lack target treatments. Therefore, in order to identify potential targets for ESCC treatment, we carried out a transcriptome analysis with ESCC and paired nonmalignant surrounding mucosa samples, followed by a master regulator analysis, and further explored the role of the identified central regulatory genes through in vivo and in vitro assays. Among the transcription factors deregulated/enriched in ESCC, we focused on FOXM1 because of its involvement in the regulation of critical biological processes. A new transcriptome analysis performed with ESCC cell lineage TE-1 showed that the modulation of FOXM1 expression resulted in PIK3R3 expression changes, whereas chromatin immunoprecipitation assay revealed that FOXM1 was capable of binding onto PIK3R3 promoter, thus demonstrating that PIK3R3 is a new FOXM1 target. Furthermore, FOXM1 overexpression resulted in the activation of PIK3/AKT signaling pathway through PIK3R3-mediated AKT phosphorylation. Finally, the analysis of the clinic-pathological data of ESCC patients revealed that overexpression of both FOXM1 and PIK3R3 was associated with poor prognosis, but only the latter was an independent prognosis factor for ESCC patients. In conclusion, our results show that FOXM1 seems to play a central role in ESCC carcinogenesis by upregulating many oncogenes found overexpressed in this tumor. Furthermore, PIK3R3 is a novel FOXM1 target that triggers the activation of the PI3K/AKT pathway in ESCC cells.
format Online
Article
Text
id pubmed-5908275
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Impact Journals LLC
record_format MEDLINE/PubMed
spelling pubmed-59082752018-04-20 Esophageal squamous cell carcinoma transcriptome reveals the effect of FOXM1 on patient outcome through novel PIK3R3 mediated activation of PI3K signaling pathway Nicolau-Neto, Pedro Da Costa, Nathalia Meireles de Souza Santos, Paulo Thiago Gonzaga, Isabela Martins Ferreira, Maria Aparecida Guaraldi, Simone Moreira, Miguel Angelo Seuánez, Hector N. Brewer, Lilian Bergmann, Anke Boroni, Mariana Mencalha, Andre Luiz Kruel, Cleber Dario Pinto Lima, Sheila Coelho Soares Esposito, Dominic Simão, Tatiana Almeida Pinto, Luis Felipe Ribeiro Oncotarget Research Paper Esophageal squamous cell carcinoma (ESCC) presents poor prognosis, and patients diagnosed with this tumor currently lack target treatments. Therefore, in order to identify potential targets for ESCC treatment, we carried out a transcriptome analysis with ESCC and paired nonmalignant surrounding mucosa samples, followed by a master regulator analysis, and further explored the role of the identified central regulatory genes through in vivo and in vitro assays. Among the transcription factors deregulated/enriched in ESCC, we focused on FOXM1 because of its involvement in the regulation of critical biological processes. A new transcriptome analysis performed with ESCC cell lineage TE-1 showed that the modulation of FOXM1 expression resulted in PIK3R3 expression changes, whereas chromatin immunoprecipitation assay revealed that FOXM1 was capable of binding onto PIK3R3 promoter, thus demonstrating that PIK3R3 is a new FOXM1 target. Furthermore, FOXM1 overexpression resulted in the activation of PIK3/AKT signaling pathway through PIK3R3-mediated AKT phosphorylation. Finally, the analysis of the clinic-pathological data of ESCC patients revealed that overexpression of both FOXM1 and PIK3R3 was associated with poor prognosis, but only the latter was an independent prognosis factor for ESCC patients. In conclusion, our results show that FOXM1 seems to play a central role in ESCC carcinogenesis by upregulating many oncogenes found overexpressed in this tumor. Furthermore, PIK3R3 is a novel FOXM1 target that triggers the activation of the PI3K/AKT pathway in ESCC cells. Impact Journals LLC 2018-03-30 /pmc/articles/PMC5908275/ /pubmed/29682174 http://dx.doi.org/10.18632/oncotarget.24621 Text en Copyright: © 2018 Nicolau-Neto et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper
Nicolau-Neto, Pedro
Da Costa, Nathalia Meireles
de Souza Santos, Paulo Thiago
Gonzaga, Isabela Martins
Ferreira, Maria Aparecida
Guaraldi, Simone
Moreira, Miguel Angelo
Seuánez, Hector N.
Brewer, Lilian
Bergmann, Anke
Boroni, Mariana
Mencalha, Andre Luiz
Kruel, Cleber Dario Pinto
Lima, Sheila Coelho Soares
Esposito, Dominic
Simão, Tatiana Almeida
Pinto, Luis Felipe Ribeiro
Esophageal squamous cell carcinoma transcriptome reveals the effect of FOXM1 on patient outcome through novel PIK3R3 mediated activation of PI3K signaling pathway
title Esophageal squamous cell carcinoma transcriptome reveals the effect of FOXM1 on patient outcome through novel PIK3R3 mediated activation of PI3K signaling pathway
title_full Esophageal squamous cell carcinoma transcriptome reveals the effect of FOXM1 on patient outcome through novel PIK3R3 mediated activation of PI3K signaling pathway
title_fullStr Esophageal squamous cell carcinoma transcriptome reveals the effect of FOXM1 on patient outcome through novel PIK3R3 mediated activation of PI3K signaling pathway
title_full_unstemmed Esophageal squamous cell carcinoma transcriptome reveals the effect of FOXM1 on patient outcome through novel PIK3R3 mediated activation of PI3K signaling pathway
title_short Esophageal squamous cell carcinoma transcriptome reveals the effect of FOXM1 on patient outcome through novel PIK3R3 mediated activation of PI3K signaling pathway
title_sort esophageal squamous cell carcinoma transcriptome reveals the effect of foxm1 on patient outcome through novel pik3r3 mediated activation of pi3k signaling pathway
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5908275/
https://www.ncbi.nlm.nih.gov/pubmed/29682174
http://dx.doi.org/10.18632/oncotarget.24621
work_keys_str_mv AT nicolaunetopedro esophagealsquamouscellcarcinomatranscriptomerevealstheeffectoffoxm1onpatientoutcomethroughnovelpik3r3mediatedactivationofpi3ksignalingpathway
AT dacostanathaliameireles esophagealsquamouscellcarcinomatranscriptomerevealstheeffectoffoxm1onpatientoutcomethroughnovelpik3r3mediatedactivationofpi3ksignalingpathway
AT desouzasantospaulothiago esophagealsquamouscellcarcinomatranscriptomerevealstheeffectoffoxm1onpatientoutcomethroughnovelpik3r3mediatedactivationofpi3ksignalingpathway
AT gonzagaisabelamartins esophagealsquamouscellcarcinomatranscriptomerevealstheeffectoffoxm1onpatientoutcomethroughnovelpik3r3mediatedactivationofpi3ksignalingpathway
AT ferreiramariaaparecida esophagealsquamouscellcarcinomatranscriptomerevealstheeffectoffoxm1onpatientoutcomethroughnovelpik3r3mediatedactivationofpi3ksignalingpathway
AT guaraldisimone esophagealsquamouscellcarcinomatranscriptomerevealstheeffectoffoxm1onpatientoutcomethroughnovelpik3r3mediatedactivationofpi3ksignalingpathway
AT moreiramiguelangelo esophagealsquamouscellcarcinomatranscriptomerevealstheeffectoffoxm1onpatientoutcomethroughnovelpik3r3mediatedactivationofpi3ksignalingpathway
AT seuanezhectorn esophagealsquamouscellcarcinomatranscriptomerevealstheeffectoffoxm1onpatientoutcomethroughnovelpik3r3mediatedactivationofpi3ksignalingpathway
AT brewerlilian esophagealsquamouscellcarcinomatranscriptomerevealstheeffectoffoxm1onpatientoutcomethroughnovelpik3r3mediatedactivationofpi3ksignalingpathway
AT bergmannanke esophagealsquamouscellcarcinomatranscriptomerevealstheeffectoffoxm1onpatientoutcomethroughnovelpik3r3mediatedactivationofpi3ksignalingpathway
AT boronimariana esophagealsquamouscellcarcinomatranscriptomerevealstheeffectoffoxm1onpatientoutcomethroughnovelpik3r3mediatedactivationofpi3ksignalingpathway
AT mencalhaandreluiz esophagealsquamouscellcarcinomatranscriptomerevealstheeffectoffoxm1onpatientoutcomethroughnovelpik3r3mediatedactivationofpi3ksignalingpathway
AT kruelcleberdariopinto esophagealsquamouscellcarcinomatranscriptomerevealstheeffectoffoxm1onpatientoutcomethroughnovelpik3r3mediatedactivationofpi3ksignalingpathway
AT limasheilacoelhosoares esophagealsquamouscellcarcinomatranscriptomerevealstheeffectoffoxm1onpatientoutcomethroughnovelpik3r3mediatedactivationofpi3ksignalingpathway
AT espositodominic esophagealsquamouscellcarcinomatranscriptomerevealstheeffectoffoxm1onpatientoutcomethroughnovelpik3r3mediatedactivationofpi3ksignalingpathway
AT simaotatianaalmeida esophagealsquamouscellcarcinomatranscriptomerevealstheeffectoffoxm1onpatientoutcomethroughnovelpik3r3mediatedactivationofpi3ksignalingpathway
AT pintoluisfeliperibeiro esophagealsquamouscellcarcinomatranscriptomerevealstheeffectoffoxm1onpatientoutcomethroughnovelpik3r3mediatedactivationofpi3ksignalingpathway