Scientific Reports (Aug 2018)

PR-LncRNA signature regulates glioma cell activity through expression of SOX factors

  • Sergio Torres-Bayona,
  • Paula Aldaz,
  • Jaione Auzmendi-Iriarte,
  • Ander Saenz-Antoñanzas,
  • Idoia Garcia,
  • Mariano Arrazola,
  • Daniela Gerovska,
  • Jose Undabeitia,
  • Arrate Querejeta,
  • Larraitz Egaña,
  • Jorge Villanúa,
  • Irune Ruiz,
  • Cristina Sarasqueta,
  • Enrique Urculo,
  • Marcos J. Araúzo-Bravo,
  • Maite Huarte,
  • Nicolas Samprón,
  • Ander Matheu

DOI
https://doi.org/10.1038/s41598-018-30836-5
Journal volume & issue
Vol. 8, no. 1
pp. 1 – 12

Abstract

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Abstract Long non-coding RNAs (LncRNAs) have emerged as a relevant class of genome regulators involved in a broad range of biological processes and with important roles in tumor initiation and malignant progression. We have previously identified a p53-regulated tumor suppressor signature of LncRNAs (PR-LncRNAs) in colorectal cancer. Our aim was to identify the expression and function of this signature in gliomas. We found that the expression of the four PR-LncRNAs tested was high in human low-grade glioma samples and diminished with increasing grade of disease, being the lowest in glioblastoma samples. Functional assays demonstrated that PR-LncRNA silencing increased glioma cell proliferation and oncosphere formation. Mechanistically, we found an inverse correlation between PR-LncRNA expression and SOX1, SOX2 and SOX9 stem cell factors in human glioma biopsies and in glioma cells in vitro. Moreover, knock-down of SOX activity abolished the effect of PR-LncRNA silencing in glioma cell activity. In conclusion, our results demonstrate that the expression and function of PR-LncRNAs are significantly altered in gliomagenesis and that their activity is mediated by SOX factors. These results may provide important insights into the mechanisms responsible for glioblastoma pathogenesis.