PIMREG expression level predicts glioblastoma patient survival and affects temozolomide resistance and DNA damage response
Autor(a) principal: | |
---|---|
Data de Publicação: | 2022 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.bbadis.2022.166382 http://hdl.handle.net/11449/234282 |
Resumo: | PIMREG expression strongly correlates with cellular proliferation in both malignant and normal cells. Throughout embryo development, PIMREG expression is prominent in the central nervous system. Recent studies have described elevated PIMREG expression in different types of tumors, which correlates with patient survival and tumor aggressiveness. Given the emerging significance of PIMREG in carcinogenesis and its putative role in the context of the nervous system, we investigated the expression and function of PIMREG in gliomas, the most common primary brain tumors. We performed an extensive analysis of PIMREG expression in tumors samples from glioma patients. We then assessed the effects of PIMREG silencing and overexpression on the sensitivity of glioblastoma cell lines treated with genotoxic agents commonly used for treating patients and assessed for treatment response, proliferation and migration. Our analysis shows that glioblastoma exhibits the highest levels of PIMREG expression among all cancers analyzed and that elevated PIMREG expression is a biomarker for glioma progression and patient outcome. Moreover, PIMREG is induced by genotoxic agents, and its silencing renders glioblastoma cells sensitive to temozolomide treatment and affects ATR- and ATM-dependent signaling. Our data demonstrate that PIMREG is involved in DNA damage response and temozolomide resistance of glioblastoma cells and further supports a role for PIMREG in tumorigenesis. |
id |
UNSP_ff59d136cfd2ac98b45f367cd79e90bf |
---|---|
oai_identifier_str |
oai:repositorio.unesp.br:11449/234282 |
network_acronym_str |
UNSP |
network_name_str |
Repositório Institucional da UNESP |
repository_id_str |
2946 |
spelling |
PIMREG expression level predicts glioblastoma patient survival and affects temozolomide resistance and DNA damage responseATMATRDNA damage responseGBMGliomasTemozolomide resistancePIMREG expression strongly correlates with cellular proliferation in both malignant and normal cells. Throughout embryo development, PIMREG expression is prominent in the central nervous system. Recent studies have described elevated PIMREG expression in different types of tumors, which correlates with patient survival and tumor aggressiveness. Given the emerging significance of PIMREG in carcinogenesis and its putative role in the context of the nervous system, we investigated the expression and function of PIMREG in gliomas, the most common primary brain tumors. We performed an extensive analysis of PIMREG expression in tumors samples from glioma patients. We then assessed the effects of PIMREG silencing and overexpression on the sensitivity of glioblastoma cell lines treated with genotoxic agents commonly used for treating patients and assessed for treatment response, proliferation and migration. Our analysis shows that glioblastoma exhibits the highest levels of PIMREG expression among all cancers analyzed and that elevated PIMREG expression is a biomarker for glioma progression and patient outcome. Moreover, PIMREG is induced by genotoxic agents, and its silencing renders glioblastoma cells sensitive to temozolomide treatment and affects ATR- and ATM-dependent signaling. Our data demonstrate that PIMREG is involved in DNA damage response and temozolomide resistance of glioblastoma cells and further supports a role for PIMREG in tumorigenesis.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Department of Cellular and Molecular Biology and Pathogenic Bioagents Ribeirão Preto Medical School University of São Paulo (FMRP-USP), São PauloDepartment of Genetics Ribeirão Preto Medical School University of São Paulo (FMRP-USP), São PauloSchool of Pharmaceutical Sciences São Paulo State University (UNESP), São PauloSchool of Pharmaceutical Sciences São Paulo State University (UNESP), São PauloFAPESP: 2019/26035-1Universidade de São Paulo (USP)Universidade Estadual Paulista (UNESP)Serafim, Rodolfo BortolozoCardoso, CibeleArfelli, Vanessa CristinaValente, Valeria [UNESP]Archangelo, Leticia Fröhlich2022-05-01T15:46:12Z2022-05-01T15:46:12Z2022-06-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.bbadis.2022.166382Biochimica et Biophysica Acta - Molecular Basis of Disease, v. 1868, n. 6, 2022.1879-260X0925-4439http://hdl.handle.net/11449/23428210.1016/j.bbadis.2022.1663822-s2.0-85126615335Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengBiochimica et Biophysica Acta - Molecular Basis of Diseaseinfo:eu-repo/semantics/openAccess2024-06-21T15:18:12Zoai:repositorio.unesp.br:11449/234282Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T14:00:34.607949Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
PIMREG expression level predicts glioblastoma patient survival and affects temozolomide resistance and DNA damage response |
title |
PIMREG expression level predicts glioblastoma patient survival and affects temozolomide resistance and DNA damage response |
spellingShingle |
PIMREG expression level predicts glioblastoma patient survival and affects temozolomide resistance and DNA damage response Serafim, Rodolfo Bortolozo ATM ATR DNA damage response GBM Gliomas Temozolomide resistance |
title_short |
PIMREG expression level predicts glioblastoma patient survival and affects temozolomide resistance and DNA damage response |
title_full |
PIMREG expression level predicts glioblastoma patient survival and affects temozolomide resistance and DNA damage response |
title_fullStr |
PIMREG expression level predicts glioblastoma patient survival and affects temozolomide resistance and DNA damage response |
title_full_unstemmed |
PIMREG expression level predicts glioblastoma patient survival and affects temozolomide resistance and DNA damage response |
title_sort |
PIMREG expression level predicts glioblastoma patient survival and affects temozolomide resistance and DNA damage response |
author |
Serafim, Rodolfo Bortolozo |
author_facet |
Serafim, Rodolfo Bortolozo Cardoso, Cibele Arfelli, Vanessa Cristina Valente, Valeria [UNESP] Archangelo, Leticia Fröhlich |
author_role |
author |
author2 |
Cardoso, Cibele Arfelli, Vanessa Cristina Valente, Valeria [UNESP] Archangelo, Leticia Fröhlich |
author2_role |
author author author author |
dc.contributor.none.fl_str_mv |
Universidade de São Paulo (USP) Universidade Estadual Paulista (UNESP) |
dc.contributor.author.fl_str_mv |
Serafim, Rodolfo Bortolozo Cardoso, Cibele Arfelli, Vanessa Cristina Valente, Valeria [UNESP] Archangelo, Leticia Fröhlich |
dc.subject.por.fl_str_mv |
ATM ATR DNA damage response GBM Gliomas Temozolomide resistance |
topic |
ATM ATR DNA damage response GBM Gliomas Temozolomide resistance |
description |
PIMREG expression strongly correlates with cellular proliferation in both malignant and normal cells. Throughout embryo development, PIMREG expression is prominent in the central nervous system. Recent studies have described elevated PIMREG expression in different types of tumors, which correlates with patient survival and tumor aggressiveness. Given the emerging significance of PIMREG in carcinogenesis and its putative role in the context of the nervous system, we investigated the expression and function of PIMREG in gliomas, the most common primary brain tumors. We performed an extensive analysis of PIMREG expression in tumors samples from glioma patients. We then assessed the effects of PIMREG silencing and overexpression on the sensitivity of glioblastoma cell lines treated with genotoxic agents commonly used for treating patients and assessed for treatment response, proliferation and migration. Our analysis shows that glioblastoma exhibits the highest levels of PIMREG expression among all cancers analyzed and that elevated PIMREG expression is a biomarker for glioma progression and patient outcome. Moreover, PIMREG is induced by genotoxic agents, and its silencing renders glioblastoma cells sensitive to temozolomide treatment and affects ATR- and ATM-dependent signaling. Our data demonstrate that PIMREG is involved in DNA damage response and temozolomide resistance of glioblastoma cells and further supports a role for PIMREG in tumorigenesis. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-05-01T15:46:12Z 2022-05-01T15:46:12Z 2022-06-01 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1016/j.bbadis.2022.166382 Biochimica et Biophysica Acta - Molecular Basis of Disease, v. 1868, n. 6, 2022. 1879-260X 0925-4439 http://hdl.handle.net/11449/234282 10.1016/j.bbadis.2022.166382 2-s2.0-85126615335 |
url |
http://dx.doi.org/10.1016/j.bbadis.2022.166382 http://hdl.handle.net/11449/234282 |
identifier_str_mv |
Biochimica et Biophysica Acta - Molecular Basis of Disease, v. 1868, n. 6, 2022. 1879-260X 0925-4439 10.1016/j.bbadis.2022.166382 2-s2.0-85126615335 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Biochimica et Biophysica Acta - Molecular Basis of Disease |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1808128302935703552 |