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<p>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. </p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月28日

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  • Antonio C. Fuentes-Fayos,
  • Miguel E. G-García,
  • Teresa Sánchez-Medianero,
  • John Apps,
  • Álvaro Flores-Martínez,
  • Ana S. De la Rosa-Herencia,
  • Ignacio Gil-Duque,
  • Georg Otto,
  • Eva Venegas-Moreno,
  • Eugenio Cárdenas Ruiz-Valdepeñas,
  • Aura D. Herrera-Martínez,
  • Juan Solivera,
  • Manuel D. Gahete,
  • David A. Cano,
  • Rosa Ortega,
  • Alfonso Soto-Moreno,
  • María A. Gálvez-Moreno,
  • Juan Pedro Martínez-Barberá,
  • Raúl M. Luque

摘要

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.