Publication: Splicing Machinery is Dysregulated in Pituitary Neuroendocrine Tumors and is Associated with Aggressiveness Features.
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Identifiers
Date
2019-09-23
Authors
Vazquez-Borrego, Mari C
Fuentes-Fayos, Antonio C
Venegas-Moreno, Eva
Rivero-Cortes, Esther
Dios, Elena
Moreno-Moreno, Paloma
Madrazo-Atutxa, Ainara
Remon, Pablo
Solivera, Juan
Wildemberg, Luiz E
Advisors
Journal Title
Journal ISSN
Volume Title
Publisher
MDPI
Abstract
Pituitary neuroendocrine tumors (PitNETs) constitute approximately 15% of all brain tumors, and most have a sporadic origin. Recent studies suggest that altered alternative splicing and, consequently, appearance of aberrant splicing variants, is a common feature of most tumor pathologies. Moreover, spliceosome is considered an attractive therapeutic target in tumor pathologies, and the inhibition of SF3B1 (e.g., using pladienolide-B) has been shown to exert antitumor effects. Therefore, we aimed to analyze the expression levels of selected splicing-machinery components in 261 PitNETs (somatotropinomas/non-functioning PitNETS/corticotropinomas/prolactinomas) and evaluated the direct effects of pladienolide-B in cell proliferation/viability/hormone secretion in human PitNETs cell cultures and pituitary cell lines (AtT-20/GH3). Results revealed a severe dysregulation of splicing-machinery components in all the PitNET subtypes compared to normal pituitaries and a unique fingerprint of splicing-machinery components that accurately discriminate between normal and tumor tissue in each PitNET subtype. Moreover, expression of specific components was associated with key clinical parameters. Interestingly, certain components were commonly dysregulated throughout all PitNET subtypes. Finally, pladienolide-B reduced cell proliferation/viability/hormone secretion in PitNET cell cultures and cell lines. Altogether, our data demonstrate a drastic dysregulation of the splicing-machinery in PitNETs that might be associated to their tumorigenesis, paving the way to explore the use of specific splicing-machinery components as novel diagnostic/prognostic and therapeutic targets in PitNETs.
Description
MeSH Terms
Spliceosomes
Neuroendocrine tumors
Alternative splicing
Prolactinoma
Cell line
Hormones
Neuroendocrine tumors
Alternative splicing
Prolactinoma
Cell line
Hormones
DeCS Terms
Empalme alternativo
Empalmosomas
Hormonas
Línea celular
Prolactinoma
Tumores neuroendocrinos
Empalmosomas
Hormonas
Línea celular
Prolactinoma
Tumores neuroendocrinos
CIE Terms
Keywords
Pituitary neuroendocrine tumors, Pladienolide-B., Spliceosome, Splicing
Citation
Vázquez-Borrego MC, Fuentes-Fayos AC, Venegas-Moreno E, Rivero-Cortés E, Dios E, Moreno-Moreno P, et al. Splicing Machinery is Dysregulated in Pituitary Neuroendocrine Tumors and is Associated with Aggressiveness Features. Cancers (Basel). 2019 Sep 26;11(10):1439