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

• Published in: Acta neuropathologica communications Vol. 13; no. 1; pp. 142 - 21
• Main Authors: Fuentes-Fayos, Antonio C., G-García, Miguel E., Sánchez-Medianero, Teresa, Apps, John, Flores-Martínez, Álvaro, De la Rosa-Herencia, Ana S., Gil-Duque, Ignacio, Otto, Georg, Venegas-Moreno, Eva, Ruiz-Valdepeñas, Eugenio Cárdenas, Herrera-Martínez, Aura D., Solivera, Juan, Gahete, Manuel D., Cano, David A., Ortega, Rosa, Soto-Moreno, Alfonso, Gálvez-Moreno, María A., Martínez-Barberá, Juan Pedro, Luque, Raúl M.
• Format: Journal Article
• Language: English
• Published: London BioMed Central 28.06.2025; BioMed Central Ltd; BMC
• Subjects: Adult; Antitumour therapy; Biological markers; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Biomedical and Life Sciences; Biomedicine; Care and treatment; Craniopharyngioma; Craniopharyngioma - genetics; Craniopharyngioma - metabolism; Craniopharyngioma - pathology; Diagnosis; Female; Health aspects; Humans; Male; Middle Aged; Neurology; Neurosciences; Pathology; Pituitary gland tumors; Pituitary Neoplasms - genetics; Pituitary Neoplasms - metabolism; Pituitary Neoplasms - pathology; Prognosis; PRPF8; RAVER1; RNA Splicing; RNA Splicing Factors - genetics; RNA Splicing Factors - metabolism; RNA-Binding Proteins; Serine-Arginine Splicing Factors - genetics; Serine-Arginine Splicing Factors - metabolism; Spliceosome components; Spliceosomes - metabolism; Splicing factors; Spain; Canada; Taiwan; RAVER1; Antitumour therapy; Craniopharyngioma; Spliceosome components; Splicing factors; PRPF8; Pladienolide B
• ISSN: 2051-5960; 2051-5960
• DOI: 10.1186/s40478-025-02040-w

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.