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
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/139708

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oai_identifier_str oai:sedici.unlp.edu.ar:10915/139708
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repository_id_str 1329
network_name_str SEDICI (UNLP)
spelling 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 info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.format.none.fl_str_mv application/pdf
143-151
dc.source.none.fl_str_mv reponame:SEDICI (UNLP)
instname:Universidad Nacional de La Plata
instacron:UNLP
reponame_str SEDICI (UNLP)
collection SEDICI (UNLP)
instname_str Universidad Nacional de La Plata
instacron_str UNLP
institution UNLP
repository.name.fl_str_mv SEDICI (UNLP) - Universidad Nacional de La Plata
repository.mail.fl_str_mv alira@sedici.unlp.edu.ar
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