Up-regulation of tumor necrosis factor-α pathway survival genes and of the receptor TNFR2 in gastric cancer
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.4251/wjgo.v11.i4.281 http://hdl.handle.net/11449/189115 |
Resumo: | BACKGROUND Gastric carcinogenesis can be induced by chronic inflammation triggered by Helicobacter pylori (H. pylori) infection. Tumor necrosis factor (TNF)-α and its receptors (TNFR1 and TNFR2) regulate important cellular processes, such as apoptosis and cell survival, and the disruption of which can lead to cancer. This signaling pathway is also modulated by microRNAs (miRNAs), altering gene expression. AIM To evaluate the mRNA and miRNAs expression involved in the TNF-α signaling pathway in gastric cancer (GC) tissues and its relationship. METHODS Quantitative polymerase chain reaction (qPCR) by TaqMan® assay was used to quantify the RNA transcript levels of TNF-α signaling pathway (TNF, TNFR1, TNFR2, TRADD, TRAF2, CFLIP, NFKB1, NFKB2, CASP8, CASP3) and miRNAs that targets genes from this pathway (miR-19a, miR-34a, miR-103a, miR-130a, miR-181c) in 30 GC fresh tissue samples. Molecular diagnosis of H. pylori was performed by nested PCR for gene HSP60. A miRNA:mRNA interaction network was construct using Cytoscape v3.1.1 from the in silico analysis performed using public databases. RESULTS Up-regulation of cellular survival genes as TNF, TNFR2, TRADD, TRAF2, CFLIP, and NFKB2, besides CASP8 and miR-34a was observed in GC tissues, whereas mediators of apoptosis such as TNFR1 and CASP3 were down-regulated. When the samples were stratified by histological type, the expression of miR-103a and miR-130a was significantly increased in the diffuse-type of GC compared to the intestinal-type. However, no influence of H. pylori infection was observed on the expression levels of mRNA and miRNAs analyzed. Moreover, the miRNA:mRNA interaction network showed several interrelations between the miRNAs and their target genes, highlighting miR-19a and miR-103a, which has as predicted or validated target a large number of genes in the TNF-α pathway, including TNF, TNFR1, TNFR2, CFLIP, TRADD, CASP3 and CASP8. CONCLUSION Our findings show that cell survival genes mediated by TNF/TNFR2 binding is up-regulated in GC favoring its pro-tumoral effect, while pro-apoptotic genes as CASP3 and TNFR1 are down-regulated, indicating disbalance between apoptosis and cell proliferation processes in this neoplasm. This process can also be influenced by an intricate regulatory network of miRNA:mRNA. |
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Repositório Institucional da UNESP |
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Up-regulation of tumor necrosis factor-α pathway survival genes and of the receptor TNFR2 in gastric cancerCellular survivalGastric cancerMicroRNAsTNFR1TNFR2Tumor necrosis factor-α signalingBACKGROUND Gastric carcinogenesis can be induced by chronic inflammation triggered by Helicobacter pylori (H. pylori) infection. Tumor necrosis factor (TNF)-α and its receptors (TNFR1 and TNFR2) regulate important cellular processes, such as apoptosis and cell survival, and the disruption of which can lead to cancer. This signaling pathway is also modulated by microRNAs (miRNAs), altering gene expression. AIM To evaluate the mRNA and miRNAs expression involved in the TNF-α signaling pathway in gastric cancer (GC) tissues and its relationship. METHODS Quantitative polymerase chain reaction (qPCR) by TaqMan® assay was used to quantify the RNA transcript levels of TNF-α signaling pathway (TNF, TNFR1, TNFR2, TRADD, TRAF2, CFLIP, NFKB1, NFKB2, CASP8, CASP3) and miRNAs that targets genes from this pathway (miR-19a, miR-34a, miR-103a, miR-130a, miR-181c) in 30 GC fresh tissue samples. Molecular diagnosis of H. pylori was performed by nested PCR for gene HSP60. A miRNA:mRNA interaction network was construct using Cytoscape v3.1.1 from the in silico analysis performed using public databases. RESULTS Up-regulation of cellular survival genes as TNF, TNFR2, TRADD, TRAF2, CFLIP, and NFKB2, besides CASP8 and miR-34a was observed in GC tissues, whereas mediators of apoptosis such as TNFR1 and CASP3 were down-regulated. When the samples were stratified by histological type, the expression of miR-103a and miR-130a was significantly increased in the diffuse-type of GC compared to the intestinal-type. However, no influence of H. pylori infection was observed on the expression levels of mRNA and miRNAs analyzed. Moreover, the miRNA:mRNA interaction network showed several interrelations between the miRNAs and their target genes, highlighting miR-19a and miR-103a, which has as predicted or validated target a large number of genes in the TNF-α pathway, including TNF, TNFR1, TNFR2, CFLIP, TRADD, CASP3 and CASP8. CONCLUSION Our findings show that cell survival genes mediated by TNF/TNFR2 binding is up-regulated in GC favoring its pro-tumoral effect, while pro-apoptotic genes as CASP3 and TNFR1 are down-regulated, indicating disbalance between apoptosis and cell proliferation processes in this neoplasm. This process can also be influenced by an intricate regulatory network of miRNA:mRNA.Department of Biology São Paulo State University - UNESPDepartment of Surgery and Orthopedics Faculty of Medicine São Paulo State University - UNESPDepartment of Biology São Paulo State University - UNESPDepartment of Surgery and Orthopedics Faculty of Medicine São Paulo State University - UNESPUniversidade Estadual Paulista (Unesp)Rossi, Ana Flávia Teixeira [UNESP]Contiero, Júlia Cocenzo [UNESP]Manoel-Caetano, Fernanda da Silva [UNESP]Severino, Fábio Eduardo [UNESP]Silva, Ana Elizabete [UNESP]2019-10-06T16:30:17Z2019-10-06T16:30:17Z2019-04-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article281-294http://dx.doi.org/10.4251/wjgo.v11.i4.281World Journal of Gastrointestinal Oncology, v. 11, n. 4, p. 281-294, 2019.1948-5204http://hdl.handle.net/11449/18911510.4251/wjgo.v11.i4.2812-s2.0-85065618317Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengWorld Journal of Gastrointestinal Oncologyinfo:eu-repo/semantics/openAccess2024-08-14T14:19:43Zoai:repositorio.unesp.br:11449/189115Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-14T14:19:43Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Up-regulation of tumor necrosis factor-α pathway survival genes and of the receptor TNFR2 in gastric cancer |
title |
Up-regulation of tumor necrosis factor-α pathway survival genes and of the receptor TNFR2 in gastric cancer |
spellingShingle |
Up-regulation of tumor necrosis factor-α pathway survival genes and of the receptor TNFR2 in gastric cancer Rossi, Ana Flávia Teixeira [UNESP] Cellular survival Gastric cancer MicroRNAs TNFR1 TNFR2 Tumor necrosis factor-α signaling |
title_short |
Up-regulation of tumor necrosis factor-α pathway survival genes and of the receptor TNFR2 in gastric cancer |
title_full |
Up-regulation of tumor necrosis factor-α pathway survival genes and of the receptor TNFR2 in gastric cancer |
title_fullStr |
Up-regulation of tumor necrosis factor-α pathway survival genes and of the receptor TNFR2 in gastric cancer |
title_full_unstemmed |
Up-regulation of tumor necrosis factor-α pathway survival genes and of the receptor TNFR2 in gastric cancer |
title_sort |
Up-regulation of tumor necrosis factor-α pathway survival genes and of the receptor TNFR2 in gastric cancer |
author |
Rossi, Ana Flávia Teixeira [UNESP] |
author_facet |
Rossi, Ana Flávia Teixeira [UNESP] Contiero, Júlia Cocenzo [UNESP] Manoel-Caetano, Fernanda da Silva [UNESP] Severino, Fábio Eduardo [UNESP] Silva, Ana Elizabete [UNESP] |
author_role |
author |
author2 |
Contiero, Júlia Cocenzo [UNESP] Manoel-Caetano, Fernanda da Silva [UNESP] Severino, Fábio Eduardo [UNESP] Silva, Ana Elizabete [UNESP] |
author2_role |
author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Rossi, Ana Flávia Teixeira [UNESP] Contiero, Júlia Cocenzo [UNESP] Manoel-Caetano, Fernanda da Silva [UNESP] Severino, Fábio Eduardo [UNESP] Silva, Ana Elizabete [UNESP] |
dc.subject.por.fl_str_mv |
Cellular survival Gastric cancer MicroRNAs TNFR1 TNFR2 Tumor necrosis factor-α signaling |
topic |
Cellular survival Gastric cancer MicroRNAs TNFR1 TNFR2 Tumor necrosis factor-α signaling |
description |
BACKGROUND Gastric carcinogenesis can be induced by chronic inflammation triggered by Helicobacter pylori (H. pylori) infection. Tumor necrosis factor (TNF)-α and its receptors (TNFR1 and TNFR2) regulate important cellular processes, such as apoptosis and cell survival, and the disruption of which can lead to cancer. This signaling pathway is also modulated by microRNAs (miRNAs), altering gene expression. AIM To evaluate the mRNA and miRNAs expression involved in the TNF-α signaling pathway in gastric cancer (GC) tissues and its relationship. METHODS Quantitative polymerase chain reaction (qPCR) by TaqMan® assay was used to quantify the RNA transcript levels of TNF-α signaling pathway (TNF, TNFR1, TNFR2, TRADD, TRAF2, CFLIP, NFKB1, NFKB2, CASP8, CASP3) and miRNAs that targets genes from this pathway (miR-19a, miR-34a, miR-103a, miR-130a, miR-181c) in 30 GC fresh tissue samples. Molecular diagnosis of H. pylori was performed by nested PCR for gene HSP60. A miRNA:mRNA interaction network was construct using Cytoscape v3.1.1 from the in silico analysis performed using public databases. RESULTS Up-regulation of cellular survival genes as TNF, TNFR2, TRADD, TRAF2, CFLIP, and NFKB2, besides CASP8 and miR-34a was observed in GC tissues, whereas mediators of apoptosis such as TNFR1 and CASP3 were down-regulated. When the samples were stratified by histological type, the expression of miR-103a and miR-130a was significantly increased in the diffuse-type of GC compared to the intestinal-type. However, no influence of H. pylori infection was observed on the expression levels of mRNA and miRNAs analyzed. Moreover, the miRNA:mRNA interaction network showed several interrelations between the miRNAs and their target genes, highlighting miR-19a and miR-103a, which has as predicted or validated target a large number of genes in the TNF-α pathway, including TNF, TNFR1, TNFR2, CFLIP, TRADD, CASP3 and CASP8. CONCLUSION Our findings show that cell survival genes mediated by TNF/TNFR2 binding is up-regulated in GC favoring its pro-tumoral effect, while pro-apoptotic genes as CASP3 and TNFR1 are down-regulated, indicating disbalance between apoptosis and cell proliferation processes in this neoplasm. This process can also be influenced by an intricate regulatory network of miRNA:mRNA. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-10-06T16:30:17Z 2019-10-06T16:30:17Z 2019-04-01 |
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/10.4251/wjgo.v11.i4.281 World Journal of Gastrointestinal Oncology, v. 11, n. 4, p. 281-294, 2019. 1948-5204 http://hdl.handle.net/11449/189115 10.4251/wjgo.v11.i4.281 2-s2.0-85065618317 |
url |
http://dx.doi.org/10.4251/wjgo.v11.i4.281 http://hdl.handle.net/11449/189115 |
identifier_str_mv |
World Journal of Gastrointestinal Oncology, v. 11, n. 4, p. 281-294, 2019. 1948-5204 10.4251/wjgo.v11.i4.281 2-s2.0-85065618317 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
World Journal of Gastrointestinal Oncology |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
281-294 |
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_ |
1808128199990706176 |