LncRNA JHDM1D-AS1 Is a Key Biomarker for Progression and Modulation of Gemcitabine Sensitivity in Bladder Cancer Cells

Detalhes bibliográficos
Autor(a) principal: Pereira, Isadora Oliveira Ansaloni
Data de Publicação: 2023
Outros Autores: da Silva, Glenda Nicioli, Almeida, Tamires Cunha, Lima, Ana Paula Braga, Sávio, André Luiz Ventura, Leite, Katia Ramos Moreira, Salvadori, Daisy Maria Fávero [UNESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.3390/molecules28052412
http://hdl.handle.net/11449/248507
Resumo: Long non-coding RNAs are frequently found to be dysregulated and are linked to carcinogenesis, aggressiveness, and chemoresistance in a variety of tumors. As expression levels of the JHDM1D gene and lncRNA JHDM1D-AS1 are altered in bladder tumors, we sought to use their combined expression to distinguish between low-and high-grade bladder tumors by RTq-PCR. In addition, we evaluated the functional role of JHDM1D-AS1 and its association with the modulation of gemcitabine sensitivity in high-grade bladder-tumor cells. J82 and UM-UC-3 cells were treated with siRNA-JHDM1D-AS1 and/or three concentrations of gemcitabine (0.39, 0.78, and 1.56 µM), and then submitted to cytotoxicity testing (XTT), clonogenic survival, cell cycle progression, cell morphology, and cell migration assays. When JHDM1D and JHDM1D-AS1 expression levels were used in combination, our findings indicated favorable prognostic value. Furthermore, the combined treatment resulted in greater cytotoxicity, a decrease in clone formation, G0/G1 cell cycle arrest, morphological alterations, and a reduction in cell migration capacity in both lineages compared to the treatments alone. Thus, silencing of JHDM1D-AS1 reduced the growth and proliferation of high-grade bladder-tumor cells and increased their sensitivity to gemcitabine treatment. In addition, the expression of JHDM1D/JHDM1D-AS1 indicated potential prognostic value in the progression of bladder tumors.
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spelling LncRNA JHDM1D-AS1 Is a Key Biomarker for Progression and Modulation of Gemcitabine Sensitivity in Bladder Cancer Cellsbladder cancerJHDM1D-AS1long non-coding RNAsLong non-coding RNAs are frequently found to be dysregulated and are linked to carcinogenesis, aggressiveness, and chemoresistance in a variety of tumors. As expression levels of the JHDM1D gene and lncRNA JHDM1D-AS1 are altered in bladder tumors, we sought to use their combined expression to distinguish between low-and high-grade bladder tumors by RTq-PCR. In addition, we evaluated the functional role of JHDM1D-AS1 and its association with the modulation of gemcitabine sensitivity in high-grade bladder-tumor cells. J82 and UM-UC-3 cells were treated with siRNA-JHDM1D-AS1 and/or three concentrations of gemcitabine (0.39, 0.78, and 1.56 µM), and then submitted to cytotoxicity testing (XTT), clonogenic survival, cell cycle progression, cell morphology, and cell migration assays. When JHDM1D and JHDM1D-AS1 expression levels were used in combination, our findings indicated favorable prognostic value. Furthermore, the combined treatment resulted in greater cytotoxicity, a decrease in clone formation, G0/G1 cell cycle arrest, morphological alterations, and a reduction in cell migration capacity in both lineages compared to the treatments alone. Thus, silencing of JHDM1D-AS1 reduced the growth and proliferation of high-grade bladder-tumor cells and increased their sensitivity to gemcitabine treatment. In addition, the expression of JHDM1D/JHDM1D-AS1 indicated potential prognostic value in the progression of bladder tumors.Pró-Reitoria de Pesquisa e Pós-Graduação, Universidade Federal de Ouro PretoUniversidade Federal de Ouro PretoDepartamento de Análises Clínicas Pharmacy School UFOP—Federal University of Ouro Preto, MGLaboratory of Pain and Signaling Butantan Institute, SPDepartamento de Odontologia Faculdade do Centro Oeste Paulista—FACOP, SPDepartamento de Ciências Médicas Universidade do Oeste Paulista—UNOESTE, SPDepartamento de Cirurgia Medical School USP—University of São Paulo, SPDepartamento de Patologia Medical School UNESP—São Paulo State University, SPDepartamento de Patologia Medical School UNESP—São Paulo State University, SPPró-Reitoria de Pesquisa e Pós-Graduação, Universidade Federal de Ouro Preto: PROPPI/UFOP Nº 03/2023Universidade Federal de Ouro Preto: PROPPI/UFOP Nº 03/2023UFOP—Federal University of Ouro PretoButantan InstituteFaculdade do Centro Oeste Paulista—FACOPUniversidade do Oeste Paulista—UNOESTEUniversidade de São Paulo (USP)Universidade Estadual Paulista (UNESP)Pereira, Isadora Oliveira Ansalonida Silva, Glenda NicioliAlmeida, Tamires CunhaLima, Ana Paula BragaSávio, André Luiz VenturaLeite, Katia Ramos MoreiraSalvadori, Daisy Maria Fávero [UNESP]2023-07-29T13:45:53Z2023-07-29T13:45:53Z2023-03-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.3390/molecules28052412Molecules, v. 28, n. 5, 2023.1420-3049http://hdl.handle.net/11449/24850710.3390/molecules280524122-s2.0-85149886329Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengMoleculesinfo:eu-repo/semantics/openAccess2024-09-03T13:18:43Zoai:repositorio.unesp.br:11449/248507Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestrepositoriounesp@unesp.bropendoar:29462024-09-03T13:18:43Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv LncRNA JHDM1D-AS1 Is a Key Biomarker for Progression and Modulation of Gemcitabine Sensitivity in Bladder Cancer Cells
title LncRNA JHDM1D-AS1 Is a Key Biomarker for Progression and Modulation of Gemcitabine Sensitivity in Bladder Cancer Cells
spellingShingle LncRNA JHDM1D-AS1 Is a Key Biomarker for Progression and Modulation of Gemcitabine Sensitivity in Bladder Cancer Cells
Pereira, Isadora Oliveira Ansaloni
bladder cancer
JHDM1D-AS1
long non-coding RNAs
title_short LncRNA JHDM1D-AS1 Is a Key Biomarker for Progression and Modulation of Gemcitabine Sensitivity in Bladder Cancer Cells
title_full LncRNA JHDM1D-AS1 Is a Key Biomarker for Progression and Modulation of Gemcitabine Sensitivity in Bladder Cancer Cells
title_fullStr LncRNA JHDM1D-AS1 Is a Key Biomarker for Progression and Modulation of Gemcitabine Sensitivity in Bladder Cancer Cells
title_full_unstemmed LncRNA JHDM1D-AS1 Is a Key Biomarker for Progression and Modulation of Gemcitabine Sensitivity in Bladder Cancer Cells
title_sort LncRNA JHDM1D-AS1 Is a Key Biomarker for Progression and Modulation of Gemcitabine Sensitivity in Bladder Cancer Cells
author Pereira, Isadora Oliveira Ansaloni
author_facet Pereira, Isadora Oliveira Ansaloni
da Silva, Glenda Nicioli
Almeida, Tamires Cunha
Lima, Ana Paula Braga
Sávio, André Luiz Ventura
Leite, Katia Ramos Moreira
Salvadori, Daisy Maria Fávero [UNESP]
author_role author
author2 da Silva, Glenda Nicioli
Almeida, Tamires Cunha
Lima, Ana Paula Braga
Sávio, André Luiz Ventura
Leite, Katia Ramos Moreira
Salvadori, Daisy Maria Fávero [UNESP]
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv UFOP—Federal University of Ouro Preto
Butantan Institute
Faculdade do Centro Oeste Paulista—FACOP
Universidade do Oeste Paulista—UNOESTE
Universidade de São Paulo (USP)
Universidade Estadual Paulista (UNESP)
dc.contributor.author.fl_str_mv Pereira, Isadora Oliveira Ansaloni
da Silva, Glenda Nicioli
Almeida, Tamires Cunha
Lima, Ana Paula Braga
Sávio, André Luiz Ventura
Leite, Katia Ramos Moreira
Salvadori, Daisy Maria Fávero [UNESP]
dc.subject.por.fl_str_mv bladder cancer
JHDM1D-AS1
long non-coding RNAs
topic bladder cancer
JHDM1D-AS1
long non-coding RNAs
description Long non-coding RNAs are frequently found to be dysregulated and are linked to carcinogenesis, aggressiveness, and chemoresistance in a variety of tumors. As expression levels of the JHDM1D gene and lncRNA JHDM1D-AS1 are altered in bladder tumors, we sought to use their combined expression to distinguish between low-and high-grade bladder tumors by RTq-PCR. In addition, we evaluated the functional role of JHDM1D-AS1 and its association with the modulation of gemcitabine sensitivity in high-grade bladder-tumor cells. J82 and UM-UC-3 cells were treated with siRNA-JHDM1D-AS1 and/or three concentrations of gemcitabine (0.39, 0.78, and 1.56 µM), and then submitted to cytotoxicity testing (XTT), clonogenic survival, cell cycle progression, cell morphology, and cell migration assays. When JHDM1D and JHDM1D-AS1 expression levels were used in combination, our findings indicated favorable prognostic value. Furthermore, the combined treatment resulted in greater cytotoxicity, a decrease in clone formation, G0/G1 cell cycle arrest, morphological alterations, and a reduction in cell migration capacity in both lineages compared to the treatments alone. Thus, silencing of JHDM1D-AS1 reduced the growth and proliferation of high-grade bladder-tumor cells and increased their sensitivity to gemcitabine treatment. In addition, the expression of JHDM1D/JHDM1D-AS1 indicated potential prognostic value in the progression of bladder tumors.
publishDate 2023
dc.date.none.fl_str_mv 2023-07-29T13:45:53Z
2023-07-29T13:45:53Z
2023-03-01
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/10.3390/molecules28052412
Molecules, v. 28, n. 5, 2023.
1420-3049
http://hdl.handle.net/11449/248507
10.3390/molecules28052412
2-s2.0-85149886329
url http://dx.doi.org/10.3390/molecules28052412
http://hdl.handle.net/11449/248507
identifier_str_mv Molecules, v. 28, n. 5, 2023.
1420-3049
10.3390/molecules28052412
2-s2.0-85149886329
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Molecules
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 repositoriounesp@unesp.br
_version_ 1810021422835171328

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