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...

Full description

Saved in:

Bibliographic Details
Published in:	Apoptosis (London) 2018-02, Vol.23 (2), p.143-151
Main Authors:	Gottardo, María Florencia, Pidre, Matías L., Zuccato, Camila, Asad, Antonela S., Imsen, Mercedes, Jaita, Gabriela, Candolfi, Marianela, Romanowski, Víctor, Seilicovich, Adriana
Format:	Article
Language:	eng
Subjects:	Apoptosis Baculovirus Biochemistry Biomedical and Life Sciences Biomedicine Brain cancer Brain tumors Cancer Research Cell Biology Cell survival Drug therapy Ethylenediaminetetraacetic acid Fluorescence Gene sequencing Gene silencing Genes Genetic engineering Genetic research Health aspects Homology Humanin mRNA Neoplasia Neoplasms Oncology Original Paper Peptides Pituitary Pituitary gland Pituitary gland tumors Reporter gene Ribonucleic acid RNA RNA-mediated interference Transfection Tumor cells Tumors Virology
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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.
ISSN:	1360-8185 1573-675X