Abstract
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.
Keywords:
Antitumour therapy; Craniopharyngioma; PRPF8; Pladienolide B; RAVER1; Spliceosome components; Splicing factors.
© 2025. The Author(s).
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Biomarkers, Tumor* / genetics
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Biomarkers, Tumor* / metabolism
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Craniopharyngioma* / genetics
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Craniopharyngioma* / metabolism
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Craniopharyngioma* / pathology
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Female
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Humans
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Male
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Middle Aged
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Pituitary Neoplasms* / genetics
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Pituitary Neoplasms* / metabolism
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Pituitary Neoplasms* / pathology
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RNA Splicing
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RNA Splicing Factors* / genetics
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RNA Splicing Factors* / metabolism
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RNA-Binding Proteins
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Serine-Arginine Splicing Factors* / genetics
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Serine-Arginine Splicing Factors* / metabolism
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Spliceosomes / metabolism
Substances
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PRPF8 protein, human
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Biomarkers, Tumor
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RNA Splicing Factors
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Serine-Arginine Splicing Factors
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RNA-Binding Proteins
Grants and funding
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BIO-0139/Junta de Andalucía
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PEER-0048-410/Junta de Andalucía
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PEER-0048-410/Junta de Andalucía
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PEER-0048-410/Junta de Andalucía
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PEER-0048-410/Junta de Andalucía
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PEER-0048-410/Junta de Andalucía
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PEER-0048-410/Junta de Andalucía
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PEER-0048-410/Junta de Andalucía
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PEER-0048-410/Junta de Andalucía
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PEER-0048-410/Junta de Andalucía
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PID2022-1381850B-I00/Ministerio de Ciencia, Innovación y Universidades
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PID2022-1381850B-I00/Ministerio de Ciencia, Innovación y Universidades
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PID2022-1381850B-I00/Ministerio de Ciencia, Innovación y Universidades
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PID2022-1381850B-I00/Ministerio de Ciencia, Innovación y Universidades
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PID2022-1381850B-I00/Ministerio de Ciencia, Innovación y Universidades
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PID2022-1381850B-I00/Ministerio de Ciencia, Innovación y Universidades
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PID2022-1381850B-I00/Ministerio de Ciencia, Innovación y Universidades
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PID2022-1381850B-I00/Ministerio de Ciencia, Innovación y Universidades
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PID2022-1381850B-I00/Ministerio de Ciencia, Innovación y Universidades
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PID2022-1381850B-I00/Ministerio de Ciencia, Innovación y Universidades