MiR-187 Targets the Androgen-Regulated Gene ALDH1A3 in Prostate Cancer

miRNAs are predicted to control the activity of approximately 60% of all protein-coding genes participating in the regulation of several cellular processes and diseases, including cancer. Recently, we have demonstrated that miR-187 is significantly downregulated in prostate cancer (PCa) and here we...

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Autores: Casanova-Salas, Irene, Masiá, Esther, Armiñán, Ana, Calatrava, Ana, Mancarella, Caterina, Rubio-Briones, José, Scotlandi, Katia, Vicent, María Jesús, López Guerrero, José Antonio
Tipo de recurso: artículo
Fecha de publicación:2015
País:España
Institución:Universidad Católica de Valencia San Vicente Mártir
Repositorio:RIUCV. Repositorio de la Universidad Católica de Valencia San Vicente Mártir
Idioma:inglés
OAI Identifier:oai:riucv.ucv.es:20.500.12466/4699
Acceso en línea:http://hdl.handle.net/20.500.12466/4699
Access Level:acceso abierto
Palabra clave:2409 Genética
3201.01 Oncología
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spelling MiR-187 Targets the Androgen-Regulated Gene ALDH1A3 in Prostate CancerCasanova-Salas, IreneMasiá, EstherArmiñán, AnaCalatrava, AnaMancarella, CaterinaRubio-Briones, JoséScotlandi, KatiaVicent, María JesúsLópez Guerrero, José Antonio2409 Genética3201.01 OncologíamiRNAs are predicted to control the activity of approximately 60% of all protein-coding genes participating in the regulation of several cellular processes and diseases, including cancer. Recently, we have demonstrated that miR-187 is significantly downregulated in prostate cancer (PCa) and here we propose a proteomic approach to identify its potential targets. For this purpose, PC-3 cells were transiently transfected with miR-187 precursor and miRNA mimic negative control. Proteins were analyzed by a two-dimensional difference gel electrophoresis (2D-DIGE) and defined as differentially regulated if the observed fold change was ±1.06. Then, MALDI-TOF MS analysis was performed after protein digestion and low abundance proteins were identified by LC–MS/MS. Peptides were identified by searching against the Expasy SWISS PROT database, and target validation was performed both in vitro by western blot and qRT-PCR and in clinical samples by qRT-PCR, immunohistochemistry and ELISA. DIGE analysis showed 9 differentially expressed spots (p<0.05) and 7 showed a down-regulated expression upon miR-187 re-introduction. Among these targets we identified aldehyde dehydrogenase 1A3 (ALDH1A3). ALDH1A3 expression was significantly downregulated in PC3, LNCaP and DU-145 cells after miR-187 re-introduction. Supporting these data, the expression of ALDH1A3 was found significantly (p<0.0001) upregulated in PCa samples and inversely correlated (p<0.0001) with miR-187 expression, its expression being directly associated with Gleason score (p = 0.05). The expression of ALDH1A3 was measured in urine samples to evaluate the predictive capability of this biomarker for the presence of PCa and, at a signification level of 10%, PSA and also ALDH1A3 were significantly associated with a positive biopsy of PCa. In conclusion, our data illustrate for the first time the role of ALDH1A3 as a miR-187 target in PCa and provide insights in the utility of using this protein as a new biomarker for PCa.20242024-10-2820152015-05-1320152015-05-13journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12466/4699reponame:RIUCV. Repositorio de la Universidad Católica de Valencia San Vicente Mártirinstname:Universidad Católica de Valencia San Vicente MártirInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:riucv.ucv.es:20.500.12466/46992026-06-19T08:32:07Z
dc.title.none.fl_str_mv MiR-187 Targets the Androgen-Regulated Gene ALDH1A3 in Prostate Cancer
title MiR-187 Targets the Androgen-Regulated Gene ALDH1A3 in Prostate Cancer
spellingShingle MiR-187 Targets the Androgen-Regulated Gene ALDH1A3 in Prostate Cancer
Casanova-Salas, Irene
2409 Genética
3201.01 Oncología
title_short MiR-187 Targets the Androgen-Regulated Gene ALDH1A3 in Prostate Cancer
title_full MiR-187 Targets the Androgen-Regulated Gene ALDH1A3 in Prostate Cancer
title_fullStr MiR-187 Targets the Androgen-Regulated Gene ALDH1A3 in Prostate Cancer
title_full_unstemmed MiR-187 Targets the Androgen-Regulated Gene ALDH1A3 in Prostate Cancer
title_sort MiR-187 Targets the Androgen-Regulated Gene ALDH1A3 in Prostate Cancer
dc.creator.none.fl_str_mv Casanova-Salas, Irene
Masiá, Esther
Armiñán, Ana
Calatrava, Ana
Mancarella, Caterina
Rubio-Briones, José
Scotlandi, Katia
Vicent, María Jesús
López Guerrero, José Antonio
author Casanova-Salas, Irene
author_facet Casanova-Salas, Irene
Masiá, Esther
Armiñán, Ana
Calatrava, Ana
Mancarella, Caterina
Rubio-Briones, José
Scotlandi, Katia
Vicent, María Jesús
López Guerrero, José Antonio
author_role author
author2 Masiá, Esther
Armiñán, Ana
Calatrava, Ana
Mancarella, Caterina
Rubio-Briones, José
Scotlandi, Katia
Vicent, María Jesús
López Guerrero, José Antonio
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv 2409 Genética
3201.01 Oncología
topic 2409 Genética
3201.01 Oncología
description miRNAs are predicted to control the activity of approximately 60% of all protein-coding genes participating in the regulation of several cellular processes and diseases, including cancer. Recently, we have demonstrated that miR-187 is significantly downregulated in prostate cancer (PCa) and here we propose a proteomic approach to identify its potential targets. For this purpose, PC-3 cells were transiently transfected with miR-187 precursor and miRNA mimic negative control. Proteins were analyzed by a two-dimensional difference gel electrophoresis (2D-DIGE) and defined as differentially regulated if the observed fold change was ±1.06. Then, MALDI-TOF MS analysis was performed after protein digestion and low abundance proteins were identified by LC–MS/MS. Peptides were identified by searching against the Expasy SWISS PROT database, and target validation was performed both in vitro by western blot and qRT-PCR and in clinical samples by qRT-PCR, immunohistochemistry and ELISA. DIGE analysis showed 9 differentially expressed spots (p<0.05) and 7 showed a down-regulated expression upon miR-187 re-introduction. Among these targets we identified aldehyde dehydrogenase 1A3 (ALDH1A3). ALDH1A3 expression was significantly downregulated in PC3, LNCaP and DU-145 cells after miR-187 re-introduction. Supporting these data, the expression of ALDH1A3 was found significantly (p<0.0001) upregulated in PCa samples and inversely correlated (p<0.0001) with miR-187 expression, its expression being directly associated with Gleason score (p = 0.05). The expression of ALDH1A3 was measured in urine samples to evaluate the predictive capability of this biomarker for the presence of PCa and, at a signification level of 10%, PSA and also ALDH1A3 were significantly associated with a positive biopsy of PCa. In conclusion, our data illustrate for the first time the role of ALDH1A3 as a miR-187 target in PCa and provide insights in the utility of using this protein as a new biomarker for PCa.
publishDate 2015
dc.date.none.fl_str_mv 2015
2015-05-13
2015
2015-05-13
2024
2024-10-28
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12466/4699
url http://hdl.handle.net/20.500.12466/4699
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:RIUCV. Repositorio de la Universidad Católica de Valencia San Vicente Mártir
instname:Universidad Católica de Valencia San Vicente Mártir
instname_str Universidad Católica de Valencia San Vicente Mártir
reponame_str RIUCV. Repositorio de la Universidad Católica de Valencia San Vicente Mártir
collection RIUCV. Repositorio de la Universidad Católica de Valencia San Vicente Mártir
repository.name.fl_str_mv
repository.mail.fl_str_mv
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