Transcriptional Up-Regulation of APE1/Ref-1 in hepatic tumor: Role in hepatocytes resistance to oxidative stress and apoptosis

Autores
Di Maso, Vittorio; Mediavilla, Maria Gabriela; Vascotto, Carlo; Lupo, Francesco; Baccarani, Umberto; Avellini, Claudio; Tell, Gianluca; Tiribelli, Claudio; Crocè, Lory Saveria
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Objective Human Hepatocellular Carcinoma (HCC) is the fifth most frequent neoplasm worldwide and the most serious complication of long-standing chronic liver diseases (CLD). Its development is associated with chronic inflammation and sustained oxidative stress. Deregulation of apurinic apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1), a master regulator of cellular response to oxidative stress, has been associated with poor prognosis in several cancers including HCC. Design In the present study we investigated the APE1/Ref-1 mRNA levels in cirrhotic and HCC tissues obtained during HCC resection. The possible protective role of APE1/Ref-1 against oxidative stress and apoptosis was evaluated in vitro in immortalized human hepatocytes (IHH) over-expressing APE1/Ref-1. Results APE1/Ref-1 was up-regulated in HCC, regulation occurring at the transcriptional level. APE1/Ref-1 mRNA content increased with the progression of liver disease with the transcriptional up-regulation present in cirrhosis significantly increased in HCC. The up-regulation was higher in the less differentiated cancers. In vitro, over-expression of APE1/Ref-1 in normal hepatocytes conferred cell protection against oxidative stress and it was associated with BAX inhibition and escape from apoptosis. Conclusion APE1/Ref-1 is up-regulated in HCC and this over-expression correlates with cancer aggressiveness. The up-regulation occurs at the transcriptional level and it is present in the earliest phases of hepatocarcinogenesis. The APE-1/Ref-1 over-expression is associated with hepatocyte survival and inhibits BAX activation and apoptosis. These data suggest a possible role of APE1/Ref-1 over-expression both in hepatocyte survival and HCC development calling attention to this molecule as a promising marker for HCC diagnosis and treatment.
Fil: Di Maso, Vittorio. Fondazione Italiana Fegato Area Science Park Basovizza; Italia
Fil: Mediavilla, Maria Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Vascotto, Carlo. Universidad de Udine; Italia
Fil: Lupo, Francesco. Universidad de Torino; Italia
Fil: Baccarani, Umberto. Universidad de Udine; Italia
Fil: Avellini, Claudio. Universidad de Udine; Italia
Fil: Tell, Gianluca. Fondazione Italiana Fegato Area Science Park Basovizza; Italia
Fil: Tiribelli, Claudio. Università degli Studi di Trieste; Italia. Fondazione Italiana Fegato Area Science Park Basovizza; Italia
Fil: Crocè, Lory Saveria. Università degli Studi di Trieste; Italia. Fondazione Italiana Fegato Area Science Park Basovizza; Italia
Materia
HEPATOCELLULAR CARCINOMA
OXIDATIVE STRESS
APOPTOSIS
CHRONIC LIVER DISEASE
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/94265
Acceder
id CONICETDig_b6430f08a7dc9f4b8736f1d844e580ea
oai_identifier_str oai:ri.conicet.gov.ar:11336/94265
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Transcriptional Up-Regulation of APE1/Ref-1 in hepatic tumor: Role in hepatocytes resistance to oxidative stress and apoptosisDi Maso, VittorioMediavilla, Maria GabrielaVascotto, CarloLupo, FrancescoBaccarani, UmbertoAvellini, ClaudioTell, GianlucaTiribelli, ClaudioCrocè, Lory SaveriaHEPATOCELLULAR CARCINOMAOXIDATIVE STRESSAPOPTOSISCHRONIC LIVER DISEASEhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Objective Human Hepatocellular Carcinoma (HCC) is the fifth most frequent neoplasm worldwide and the most serious complication of long-standing chronic liver diseases (CLD). Its development is associated with chronic inflammation and sustained oxidative stress. Deregulation of apurinic apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1), a master regulator of cellular response to oxidative stress, has been associated with poor prognosis in several cancers including HCC. Design In the present study we investigated the APE1/Ref-1 mRNA levels in cirrhotic and HCC tissues obtained during HCC resection. The possible protective role of APE1/Ref-1 against oxidative stress and apoptosis was evaluated in vitro in immortalized human hepatocytes (IHH) over-expressing APE1/Ref-1. Results APE1/Ref-1 was up-regulated in HCC, regulation occurring at the transcriptional level. APE1/Ref-1 mRNA content increased with the progression of liver disease with the transcriptional up-regulation present in cirrhosis significantly increased in HCC. The up-regulation was higher in the less differentiated cancers. In vitro, over-expression of APE1/Ref-1 in normal hepatocytes conferred cell protection against oxidative stress and it was associated with BAX inhibition and escape from apoptosis. Conclusion APE1/Ref-1 is up-regulated in HCC and this over-expression correlates with cancer aggressiveness. The up-regulation occurs at the transcriptional level and it is present in the earliest phases of hepatocarcinogenesis. The APE-1/Ref-1 over-expression is associated with hepatocyte survival and inhibits BAX activation and apoptosis. These data suggest a possible role of APE1/Ref-1 over-expression both in hepatocyte survival and HCC development calling attention to this molecule as a promising marker for HCC diagnosis and treatment.Fil: Di Maso, Vittorio. Fondazione Italiana Fegato Area Science Park Basovizza; ItaliaFil: Mediavilla, Maria Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Vascotto, Carlo. Universidad de Udine; ItaliaFil: Lupo, Francesco. Universidad de Torino; ItaliaFil: Baccarani, Umberto. Universidad de Udine; ItaliaFil: Avellini, Claudio. Universidad de Udine; ItaliaFil: Tell, Gianluca. Fondazione Italiana Fegato Area Science Park Basovizza; ItaliaFil: Tiribelli, Claudio. Università degli Studi di Trieste; Italia. Fondazione Italiana Fegato Area Science Park Basovizza; ItaliaFil: Crocè, Lory Saveria. Università degli Studi di Trieste; Italia. Fondazione Italiana Fegato Area Science Park Basovizza; ItaliaPublic Library of Science2015-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/94265Di Maso, Vittorio; Mediavilla, Maria Gabriela; Vascotto, Carlo; Lupo, Francesco; Baccarani, Umberto; et al.; Transcriptional Up-Regulation of APE1/Ref-1 in hepatic tumor: Role in hepatocytes resistance to oxidative stress and apoptosis; Public Library of Science; Plos One; 10; 12; 12-2015; 1-141932-6203CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0143289info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0143289info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-02-06T13:30:27Zoai:ri.conicet.gov.ar:11336/94265instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982026-02-06 13:30:28.053CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Transcriptional Up-Regulation of APE1/Ref-1 in hepatic tumor: Role in hepatocytes resistance to oxidative stress and apoptosis
title Transcriptional Up-Regulation of APE1/Ref-1 in hepatic tumor: Role in hepatocytes resistance to oxidative stress and apoptosis
spellingShingle Transcriptional Up-Regulation of APE1/Ref-1 in hepatic tumor: Role in hepatocytes resistance to oxidative stress and apoptosis
Di Maso, Vittorio
HEPATOCELLULAR CARCINOMA
OXIDATIVE STRESS
APOPTOSIS
CHRONIC LIVER DISEASE
title_short Transcriptional Up-Regulation of APE1/Ref-1 in hepatic tumor: Role in hepatocytes resistance to oxidative stress and apoptosis
title_full Transcriptional Up-Regulation of APE1/Ref-1 in hepatic tumor: Role in hepatocytes resistance to oxidative stress and apoptosis
title_fullStr Transcriptional Up-Regulation of APE1/Ref-1 in hepatic tumor: Role in hepatocytes resistance to oxidative stress and apoptosis
title_full_unstemmed Transcriptional Up-Regulation of APE1/Ref-1 in hepatic tumor: Role in hepatocytes resistance to oxidative stress and apoptosis
title_sort Transcriptional Up-Regulation of APE1/Ref-1 in hepatic tumor: Role in hepatocytes resistance to oxidative stress and apoptosis
dc.creator.none.fl_str_mv Di Maso, Vittorio
Mediavilla, Maria Gabriela
Vascotto, Carlo
Lupo, Francesco
Baccarani, Umberto
Avellini, Claudio
Tell, Gianluca
Tiribelli, Claudio
Crocè, Lory Saveria
author Di Maso, Vittorio
author_facet Di Maso, Vittorio
Mediavilla, Maria Gabriela
Vascotto, Carlo
Lupo, Francesco
Baccarani, Umberto
Avellini, Claudio
Tell, Gianluca
Tiribelli, Claudio
Crocè, Lory Saveria
author_role author
author2 Mediavilla, Maria Gabriela
Vascotto, Carlo
Lupo, Francesco
Baccarani, Umberto
Avellini, Claudio
Tell, Gianluca
Tiribelli, Claudio
Crocè, Lory Saveria
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv HEPATOCELLULAR CARCINOMA
OXIDATIVE STRESS
APOPTOSIS
CHRONIC LIVER DISEASE
topic HEPATOCELLULAR CARCINOMA
OXIDATIVE STRESS
APOPTOSIS
CHRONIC LIVER DISEASE
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Objective Human Hepatocellular Carcinoma (HCC) is the fifth most frequent neoplasm worldwide and the most serious complication of long-standing chronic liver diseases (CLD). Its development is associated with chronic inflammation and sustained oxidative stress. Deregulation of apurinic apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1), a master regulator of cellular response to oxidative stress, has been associated with poor prognosis in several cancers including HCC. Design In the present study we investigated the APE1/Ref-1 mRNA levels in cirrhotic and HCC tissues obtained during HCC resection. The possible protective role of APE1/Ref-1 against oxidative stress and apoptosis was evaluated in vitro in immortalized human hepatocytes (IHH) over-expressing APE1/Ref-1. Results APE1/Ref-1 was up-regulated in HCC, regulation occurring at the transcriptional level. APE1/Ref-1 mRNA content increased with the progression of liver disease with the transcriptional up-regulation present in cirrhosis significantly increased in HCC. The up-regulation was higher in the less differentiated cancers. In vitro, over-expression of APE1/Ref-1 in normal hepatocytes conferred cell protection against oxidative stress and it was associated with BAX inhibition and escape from apoptosis. Conclusion APE1/Ref-1 is up-regulated in HCC and this over-expression correlates with cancer aggressiveness. The up-regulation occurs at the transcriptional level and it is present in the earliest phases of hepatocarcinogenesis. The APE-1/Ref-1 over-expression is associated with hepatocyte survival and inhibits BAX activation and apoptosis. These data suggest a possible role of APE1/Ref-1 over-expression both in hepatocyte survival and HCC development calling attention to this molecule as a promising marker for HCC diagnosis and treatment.
Fil: Di Maso, Vittorio. Fondazione Italiana Fegato Area Science Park Basovizza; Italia
Fil: Mediavilla, Maria Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Vascotto, Carlo. Universidad de Udine; Italia
Fil: Lupo, Francesco. Universidad de Torino; Italia
Fil: Baccarani, Umberto. Universidad de Udine; Italia
Fil: Avellini, Claudio. Universidad de Udine; Italia
Fil: Tell, Gianluca. Fondazione Italiana Fegato Area Science Park Basovizza; Italia
Fil: Tiribelli, Claudio. Università degli Studi di Trieste; Italia. Fondazione Italiana Fegato Area Science Park Basovizza; Italia
Fil: Crocè, Lory Saveria. Università degli Studi di Trieste; Italia. Fondazione Italiana Fegato Area Science Park Basovizza; Italia
description Objective Human Hepatocellular Carcinoma (HCC) is the fifth most frequent neoplasm worldwide and the most serious complication of long-standing chronic liver diseases (CLD). Its development is associated with chronic inflammation and sustained oxidative stress. Deregulation of apurinic apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1), a master regulator of cellular response to oxidative stress, has been associated with poor prognosis in several cancers including HCC. Design In the present study we investigated the APE1/Ref-1 mRNA levels in cirrhotic and HCC tissues obtained during HCC resection. The possible protective role of APE1/Ref-1 against oxidative stress and apoptosis was evaluated in vitro in immortalized human hepatocytes (IHH) over-expressing APE1/Ref-1. Results APE1/Ref-1 was up-regulated in HCC, regulation occurring at the transcriptional level. APE1/Ref-1 mRNA content increased with the progression of liver disease with the transcriptional up-regulation present in cirrhosis significantly increased in HCC. The up-regulation was higher in the less differentiated cancers. In vitro, over-expression of APE1/Ref-1 in normal hepatocytes conferred cell protection against oxidative stress and it was associated with BAX inhibition and escape from apoptosis. Conclusion APE1/Ref-1 is up-regulated in HCC and this over-expression correlates with cancer aggressiveness. The up-regulation occurs at the transcriptional level and it is present in the earliest phases of hepatocarcinogenesis. The APE-1/Ref-1 over-expression is associated with hepatocyte survival and inhibits BAX activation and apoptosis. These data suggest a possible role of APE1/Ref-1 over-expression both in hepatocyte survival and HCC development calling attention to this molecule as a promising marker for HCC diagnosis and treatment.
publishDate 2015
dc.date.none.fl_str_mv 2015-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/94265
Di Maso, Vittorio; Mediavilla, Maria Gabriela; Vascotto, Carlo; Lupo, Francesco; Baccarani, Umberto; et al.; Transcriptional Up-Regulation of APE1/Ref-1 in hepatic tumor: Role in hepatocytes resistance to oxidative stress and apoptosis; Public Library of Science; Plos One; 10; 12; 12-2015; 1-14
1932-6203
CONICET Digital
CONICET
url http://hdl.handle.net/11336/94265
identifier_str_mv Di Maso, Vittorio; Mediavilla, Maria Gabriela; Vascotto, Carlo; Lupo, Francesco; Baccarani, Umberto; et al.; Transcriptional Up-Regulation of APE1/Ref-1 in hepatic tumor: Role in hepatocytes resistance to oxidative stress and apoptosis; Public Library of Science; Plos One; 10; 12; 12-2015; 1-14
1932-6203
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0143289
info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0143289
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.595271

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