Baculovirus-based gene silencing of Humanin for the treatment of pituitary tumors

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 u...

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Detalles Bibliográficos
Autores principales: Gottardo, María Florencia, Pidre, Matías Luis, Zuccato, Camila Florencia, Asad, Antonela Sofía, Imsen, Mercedes, Jaita, Gabriela, Candolfi, Marianela, Romanowski, Víctor, Seilicovich, Adriana
Formato: Articulo
Lenguaje:Inglés
Publicado: 2018
Materias:
Biología
Medicina
Humanin
Rattin
Baculovirus
ShRNA
Pituitary tumor
Apoptosis
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/139708
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-139708
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Biología
Medicina
Humanin
Rattin
Baculovirus
ShRNA
Pituitary tumor
Apoptosis
spellingShingle Biología
Medicina
Humanin
Rattin
Baculovirus
ShRNA
Pituitary tumor
Apoptosis
Gottardo, María Florencia
Pidre, Matías Luis
Zuccato, Camila Florencia
Asad, Antonela Sofía
Imsen, Mercedes
Jaita, Gabriela
Candolfi, Marianela
Romanowski, Víctor
Seilicovich, Adriana
Baculovirus-based gene silencing of Humanin for the treatment of pituitary tumors
topic_facet Biología
Medicina
Humanin
Rattin
Baculovirus
ShRNA
Pituitary tumor
Apoptosis
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.
format Articulo
Articulo
author Gottardo, María Florencia
Pidre, Matías Luis
Zuccato, Camila Florencia
Asad, Antonela Sofía
Imsen, Mercedes
Jaita, Gabriela
Candolfi, Marianela
Romanowski, Víctor
Seilicovich, Adriana
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_sort Gottardo, María Florencia
title Baculovirus-based gene silencing of Humanin for the treatment of pituitary tumors
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
publishDate 2018
url http://sedici.unlp.edu.ar/handle/10915/139708
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