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

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

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...

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Autores principales: 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
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2018
Materias:
Medicine
R
Science
Q
Acceso en línea:https://doaj.org/article/c872a6ab60e84e74817e34215cc393e2
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Sumario: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.

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