Gerovska, D. (Daniela)

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    PR-LncRNA signature regulates glioma cell activity through expression of SOX factors
    (Nature Research, 2018) Undabeitia, J. (Jose); Sampron, N. (Nicolas); Querejeta, A. (Arrate); Sarasqueta, C. (Cristina); Ruiz, I. (Irune); Gerovska, D. (Daniela); Saenz-Antoñanzas, A. (Ander); Arrazola, M. (Mariano); Garcia, I. (Idoia); Villanúa, J. (Jorge); Egaña, L. (Larraitz); Aldaz, P. (Paula); Huarte-Martínez, M. (Maite); Araúzo-Bravo, M.J. (Marcos J.); Matheu, A. (Ander); Auzmendi-Iriarte, J. (Jaione); Urculo, E. (Enrique); Torres-Bayona, S. (Sergio)
    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.