Splicing Dysregulation as Oncogenic Driver and Passenger Factor in Brain Tumors

Pamela Bielli, Vittoria Pagliarini, Marco Pieraccioli, Cinzia Caggiano, Claudio Sette*

*Autore corrispondente per questo lavoro

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

Abstract

Brain tumors are a heterogeneous group of neoplasms ranging from almost benign to highly aggressive phenotypes. The malignancy of these tumors mostly relies on gene expression reprogramming, which is frequently accompanied by the aberrant regulation of RNA processing mechanisms. In brain tumors, defects in alternative splicing result either from the dysregulation of expression and activity of splicing factors, or from mutations in the genes encoding splicing machinery components. Aberrant splicing regulation can generate dysfunctional proteins that lead to modification of fundamental physiological cellular processes, thus contributing to the development or progression of brain tumors. Herein, we summarize the current knowledge on splicing abnormalities in brain tumors and how these alterations contribute to the disease by sustaining proliferative signaling, escaping growth suppressors, or establishing a tumor microenvironment that fosters angiogenesis and intercellular communications. Lastly, we review recent efforts aimed at developing novel splicing-targeted cancer therapies, which employ oligonucleotide-based approaches or chemical modulators of alternative splicing that elicit an impact on brain tumor biology.
Lingua originaleEnglish
pagine (da-a)1-21
Numero di pagine21
RivistaCells
Volume9
DOI
Stato di pubblicazionePubblicato - 2019

Keywords

  • EGFR signaling
  • PRMT5
  • alternative splicing
  • brain tumors
  • hippo signaling
  • splicing factors
  • tumor microenvironment

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