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

Acta Neuropathol Commun. 2025 Jun 28;13(1):142. doi: 10.1186/s40478-025-02040-w.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers, Tumor* / genetics
  • Biomarkers, Tumor* / metabolism
  • Craniopharyngioma* / genetics
  • Craniopharyngioma* / metabolism
  • Craniopharyngioma* / pathology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pituitary Neoplasms* / genetics
  • Pituitary Neoplasms* / metabolism
  • Pituitary Neoplasms* / pathology
  • RNA Splicing
  • RNA Splicing Factors* / genetics
  • RNA Splicing Factors* / metabolism
  • RNA-Binding Proteins
  • Serine-Arginine Splicing Factors* / genetics
  • Serine-Arginine Splicing Factors* / metabolism
  • Spliceosomes / metabolism

Substances

  • PRPF8 protein, human
  • Biomarkers, Tumor
  • RNA Splicing Factors
  • Serine-Arginine Splicing Factors
  • RNA-Binding Proteins