Baculovirus-based gene silencing of Humanin for the treatment of pituitary tumors
- Autores
- Gottardo, María Florencia; Pidre, Matías Luis; Zuccato, Camila Florencia; Asad, Antonela Sofía; Imsen, Mercedes; Jaita, Gabriela; Candolfi, Marianela; Romanowski, Víctor; Seilicovich, Adriana
- Año de publicación
- 2018
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Pituitary tumors are the most common primary intracranial neoplasms. Humanin (HN) and Rattin (HNr), a rat homolog of HN, are short peptides with a cytoprotective action. In the present study, we aimed to evaluate whether endogenous HNr plays an antiapoptotic role in pituitary tumor cells. Thus, we used RNA interference based on short-hairpin RNA (shRNA) targeted to HNr (shHNr). A plasmid including the coding sequences for shHNr and dTomato fluorescent reporter gene was developed (pUC-shHNr). Transfection of somatolactotrope GH3 cells with pUC-shHNr increased apoptosis, suggesting that endogenous HNr plays a cytoprotective role in pituitary tumor cells. In order to evaluate the effect of blockade of endogenous HNr expression in vivo, we constructed a recombinant baculovirus (BV) encoding shHNr (BV-shHNr). In vitro, BV-shRNA was capable of transducing more than 80% of GH3 cells and decreased HNr mRNA. Also, BV-shHNr increased apoptosis in transduced GH3 cells. Intratumor injection of BV-shHNr to nude mice bearing s.c. GH3 tumors increased the number of apoptotic cells, delayed tumor growth and enhanced survival rate, suggesting that endogenous HNr may be involved in pituitary tumor progression. These preclinical data suggests that the silencing of HN expression could have a therapeutic impact on the treatment of pituitary tumors.
Instituto de Biotecnología y Biología Molecular - Materia
-
Biología
Medicina
Humanin
Rattin
Baculovirus
ShRNA
Pituitary tumor
Apoptosis - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- http://creativecommons.org/licenses/by-nc-sa/4.0/
- Repositorio
- Institución
- Universidad Nacional de La Plata
- OAI Identificador
- oai:sedici.unlp.edu.ar:10915/139708
Ver los metadatos del registro completo
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Baculovirus-based gene silencing of Humanin for the treatment of pituitary tumorsGottardo, María FlorenciaPidre, Matías LuisZuccato, Camila FlorenciaAsad, Antonela SofíaImsen, MercedesJaita, GabrielaCandolfi, MarianelaRomanowski, VíctorSeilicovich, AdrianaBiologíaMedicinaHumaninRattinBaculovirusShRNAPituitary tumorApoptosisPituitary tumors are the most common primary intracranial neoplasms. Humanin (HN) and Rattin (HNr), a rat homolog of HN, are short peptides with a cytoprotective action. In the present study, we aimed to evaluate whether endogenous HNr plays an antiapoptotic role in pituitary tumor cells. Thus, we used RNA interference based on short-hairpin RNA (shRNA) targeted to HNr (shHNr). A plasmid including the coding sequences for shHNr and dTomato fluorescent reporter gene was developed (pUC-shHNr). Transfection of somatolactotrope GH3 cells with pUC-shHNr increased apoptosis, suggesting that endogenous HNr plays a cytoprotective role in pituitary tumor cells. In order to evaluate the effect of blockade of endogenous HNr expression in vivo, we constructed a recombinant baculovirus (BV) encoding shHNr (BV-shHNr). In vitro, BV-shRNA was capable of transducing more than 80% of GH3 cells and decreased HNr mRNA. Also, BV-shHNr increased apoptosis in transduced GH3 cells. Intratumor injection of BV-shHNr to nude mice bearing s.c. GH3 tumors increased the number of apoptotic cells, delayed tumor growth and enhanced survival rate, suggesting that endogenous HNr may be involved in pituitary tumor progression. These preclinical data suggests that the silencing of HN expression could have a therapeutic impact on the treatment of pituitary tumors.Instituto de Biotecnología y Biología Molecular2018-01-19info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdf143-151http://sedici.unlp.edu.ar/handle/10915/139708enginfo:eu-repo/semantics/altIdentifier/issn/1573-675xinfo:eu-repo/semantics/altIdentifier/issn/1360-8185info:eu-repo/semantics/altIdentifier/doi/10.1007/s10495-018-1444-0info:eu-repo/semantics/altIdentifier/pmid/29352443info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-09-29T11:32:02Zoai:sedici.unlp.edu.ar:10915/139708Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-29 11:32:02.412SEDICI (UNLP) - Universidad Nacional de La Platafalse |
dc.title.none.fl_str_mv |
Baculovirus-based gene silencing of Humanin for the treatment of pituitary tumors |
title |
Baculovirus-based gene silencing of Humanin for the treatment of pituitary tumors |
spellingShingle |
Baculovirus-based gene silencing of Humanin for the treatment of pituitary tumors Gottardo, María Florencia Biología Medicina Humanin Rattin Baculovirus ShRNA Pituitary tumor Apoptosis |
title_short |
Baculovirus-based gene silencing of Humanin for the treatment of pituitary tumors |
title_full |
Baculovirus-based gene silencing of Humanin for the treatment of pituitary tumors |
title_fullStr |
Baculovirus-based gene silencing of Humanin for the treatment of pituitary tumors |
title_full_unstemmed |
Baculovirus-based gene silencing of Humanin for the treatment of pituitary tumors |
title_sort |
Baculovirus-based gene silencing of Humanin for the treatment of pituitary tumors |
dc.creator.none.fl_str_mv |
Gottardo, María Florencia Pidre, Matías Luis Zuccato, Camila Florencia Asad, Antonela Sofía Imsen, Mercedes Jaita, Gabriela Candolfi, Marianela Romanowski, Víctor Seilicovich, Adriana |
author |
Gottardo, María Florencia |
author_facet |
Gottardo, María Florencia Pidre, Matías Luis Zuccato, Camila Florencia Asad, Antonela Sofía Imsen, Mercedes Jaita, Gabriela Candolfi, Marianela Romanowski, Víctor Seilicovich, Adriana |
author_role |
author |
author2 |
Pidre, Matías Luis Zuccato, Camila Florencia Asad, Antonela Sofía Imsen, Mercedes Jaita, Gabriela Candolfi, Marianela Romanowski, Víctor Seilicovich, Adriana |
author2_role |
author author author author author author author author |
dc.subject.none.fl_str_mv |
Biología Medicina Humanin Rattin Baculovirus ShRNA Pituitary tumor Apoptosis |
topic |
Biología Medicina Humanin Rattin Baculovirus ShRNA Pituitary tumor Apoptosis |
dc.description.none.fl_txt_mv |
Pituitary tumors are the most common primary intracranial neoplasms. Humanin (HN) and Rattin (HNr), a rat homolog of HN, are short peptides with a cytoprotective action. In the present study, we aimed to evaluate whether endogenous HNr plays an antiapoptotic role in pituitary tumor cells. Thus, we used RNA interference based on short-hairpin RNA (shRNA) targeted to HNr (shHNr). A plasmid including the coding sequences for shHNr and dTomato fluorescent reporter gene was developed (pUC-shHNr). Transfection of somatolactotrope GH3 cells with pUC-shHNr increased apoptosis, suggesting that endogenous HNr plays a cytoprotective role in pituitary tumor cells. In order to evaluate the effect of blockade of endogenous HNr expression in vivo, we constructed a recombinant baculovirus (BV) encoding shHNr (BV-shHNr). In vitro, BV-shRNA was capable of transducing more than 80% of GH3 cells and decreased HNr mRNA. Also, BV-shHNr increased apoptosis in transduced GH3 cells. Intratumor injection of BV-shHNr to nude mice bearing s.c. GH3 tumors increased the number of apoptotic cells, delayed tumor growth and enhanced survival rate, suggesting that endogenous HNr may be involved in pituitary tumor progression. These preclinical data suggests that the silencing of HN expression could have a therapeutic impact on the treatment of pituitary tumors. Instituto de Biotecnología y Biología Molecular |
description |
Pituitary tumors are the most common primary intracranial neoplasms. Humanin (HN) and Rattin (HNr), a rat homolog of HN, are short peptides with a cytoprotective action. In the present study, we aimed to evaluate whether endogenous HNr plays an antiapoptotic role in pituitary tumor cells. Thus, we used RNA interference based on short-hairpin RNA (shRNA) targeted to HNr (shHNr). A plasmid including the coding sequences for shHNr and dTomato fluorescent reporter gene was developed (pUC-shHNr). Transfection of somatolactotrope GH3 cells with pUC-shHNr increased apoptosis, suggesting that endogenous HNr plays a cytoprotective role in pituitary tumor cells. In order to evaluate the effect of blockade of endogenous HNr expression in vivo, we constructed a recombinant baculovirus (BV) encoding shHNr (BV-shHNr). In vitro, BV-shRNA was capable of transducing more than 80% of GH3 cells and decreased HNr mRNA. Also, BV-shHNr increased apoptosis in transduced GH3 cells. Intratumor injection of BV-shHNr to nude mice bearing s.c. GH3 tumors increased the number of apoptotic cells, delayed tumor growth and enhanced survival rate, suggesting that endogenous HNr may be involved in pituitary tumor progression. These preclinical data suggests that the silencing of HN expression could have a therapeutic impact on the treatment of pituitary tumors. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-01-19 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Articulo 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://sedici.unlp.edu.ar/handle/10915/139708 |
url |
http://sedici.unlp.edu.ar/handle/10915/139708 |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/issn/1573-675x info:eu-repo/semantics/altIdentifier/issn/1360-8185 info:eu-repo/semantics/altIdentifier/doi/10.1007/s10495-018-1444-0 info:eu-repo/semantics/altIdentifier/pmid/29352443 |
dc.rights.none.fl_str_mv |
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openAccess |
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http://creativecommons.org/licenses/by-nc-sa/4.0/ Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) |
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