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 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.
Authors
- Raul Miguel Luque (ORCID: https://orcid.org/0000-0002-7585-1913)
- María Ángeles Gálvez-Moreno
- Aura D. Herrera‐Martínez (ORCID: https://orcid.org/0000-0003-1437-9878)
- Manuel David Gahete (ORCID: https://orcid.org/0000-0002-4578-2179)
- John Apps (ORCID: https://orcid.org/0000-0001-7902-482X)
- Georg Otto
- Antonio C. Fuentes-Fayos (ORCID: https://orcid.org/0000-0003-2069-4823)
- Eva Venegas‐Moreno
- Eugenio Cárdenas Ruiz‐Valdepeñas (ORCID: https://orcid.org/0000-0002-7488-8140)
- Miguel E. G-García (ORCID: https://orcid.org/0000-0001-6941-6715)
- David A. Cano (ORCID: https://orcid.org/0000-0001-6264-3288)
- Juan Pedro Martı́nez-Barberá (ORCID: https://orcid.org/0000-0002-5292-7276)
- Alfonso Soto‐Moreno (ORCID: https://orcid.org/0000-0002-2734-7077)
- R. Ortega (ORCID: https://orcid.org/0000-0002-0218-3299)
- Teresa Sánchez-Medianero
- Álvaro Flores‐Martínez (ORCID: https://orcid.org/0000-0002-4926-3288)
- Ignacio Gil-Duque (ORCID: https://orcid.org/0009-0000-1313-820X)
- Juan Solivera
- Ana S De la Rosa-Herencia
Institutions
- King's College London (GB)
- Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition (ES)
- Instituto Maimónides de Investigación Biomédica de Córdoba (ES)
- Hospital Universitario Reina Sofía (ES)
- Instituto de Biomedicina de Sevilla (ES)
- Genomics England (GB)
- Hospital Universitario Virgen del Rocío (ES)
- University College London (GB)
- University of Córdoba (ES)
- Cordoba University (US)
- University of Birmingham (GB)
Publication Details
- Journal
- Acta Neuropathologica Communications
- Published
- 2025-06-28
- DOI
- https://doi.org/10.1186/s40478-025-02040-w
- Primary Topic
- Cancer, Hypoxia, and Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Fundación SEEN
- Ministerio de Ciencia, Innovación y Universidades
- National Institute for Health and Care Research
- Junta de Andalucía
- Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición