Impaired splicing machinery in craniopharyngiomas unveils PRPF8 and RAVER1 as novel biomarkers and therapeutic targets

Craniopharyngiomas are rare benign pathologies but clinically challenging tumours because of their intimate relationship with critical brain structures, leading to severe endocrine-deficiencies/comorbidities. Therefore, identifying alternative prognostic/therapeutic tools is crucial. Although dysreg...

ver descrição completa

Detalhes bibliográficos
Autores: Fuentes-Fayos, Antonio C., García García, Miguel E., Sánchez-Medianero, Teresa, Apps, John, Flores-Martínez, Álvaro, Rosa-Herencia, Ana S. de la, Gil-Duque, Ignacio, Otto, Georg, Venegas Moreno, Eva, Cárdenas Ruiz-Valdepeñas, Eugenio, Herrera-Martínez, Aura D., Solivera, Juan, Gahete, Manuel D., Cano, David A., Ortega-Salas, Rosa, Soto-Moreno, Alfonso, Gálvez-Moreno, María Ángeles, Martínez-Barberá, Juan P., Luque, Raúl M.
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/400724
Acesso em linha:http://hdl.handle.net/10261/400724
https://api.elsevier.com/content/abstract/scopus_id/105009384269
Access Level:acceso abierto
Palavra-chave:Antitumour therapy
Craniopharyngioma
PRPF8
Pladienolide B
RAVER1
Spliceosome components
Splicing factors
Descrição
Resumo:Craniopharyngiomas are rare benign pathologies but clinically challenging tumours because of their intimate relationship with critical brain structures, leading to severe endocrine-deficiencies/comorbidities. Therefore, identifying alternative prognostic/therapeutic tools is crucial. Although dysregulated splicing is a molecular feature that characterizes almost all tumour/cancer types, the dysregulation of the components belonging to the molecular machinery controlling the splicing-process (spliceosome) remains unknown in craniopharyngiomas. Here, we uncover a profound dysregulation in the expression of relevant spliceosome-components and splicing-factors in craniopharyngiomas versus control non-tumour tissues, identifying PRPF8 and RAVER1 as key tumour suppressor factors associated with relevant oncogenic processes. Moreover, we demonstrate that the spliceosome activity inhibition using pladienolide-B in primary patient´s derived cell-cultures might serve as a potential therapeutic tool worth to be explored in humans. Altogether, our results demonstrate a drastic and clinically relevant spliceosome-associated molecular dysregulation in craniopharyngiomas, which could serve as a potential source of novel diagnostic/prognostic biomarkers and therapeutic targets.

Registos relacionados