PR-LncRNA signature regulates glioma cell activity through expression of SOX factors
| Autor: | M. Arrazola, Arrate Querejeta, Larraitz Egaña, Sergio Torres-Bayona, Jorge Villanua, Idoia Garcia, Cristina Sarasqueta, Jaione Auzmendi-Iriarte, Ander Saenz-Antoñanzas, Marcos J. Araúzo-Bravo, Enrique Urculo, J. Undabeitia, Daniela Gerovska, Paula Aldaz, Irune Ruiz, Nicolás Samprón, Maite Huarte, Ander Matheu |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Science Tumor initiation Biology Long non-coding RNAs (LncRNAs) adjuvant temozolomide Article 03 medical and health sciences SOX1 SOX2 Glioma transcription factors medicine Gene silencing cancer Humans concomitant long noncoding RNAs Gene Silencing Transcription factor radiotherapy SOX Transcription Factors Aged Cell Proliferation Regulation of gene expression Multidisciplinary Biological processes Brain Neoplasms pathogenesis glioblastoma Tumor suppressor STEM Middle Aged medicine.disease inhibition Gene Expression Regulation Neoplastic 030104 developmental biology Cancer research Neoplastic Stem Cells Medicine Female RNA Long Noncoding Stem cell Neoplasm Grading |
| Zdroj: | Scientific Reports, Vol 8, Iss 1, Pp 1-12 (2018) Scientific Reports Addi. Archivo Digital para la Docencia y la Investigación instname |
| ISSN: | 2045-2322 |
| Popis: | 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. PA, JA-I and AS-A were recipients of a predoctoral fellowship from the Spanish Association Against Cancer (AECC Gipuzkoa), Basque Government and Instituto Salud Carlos III. This work was supported by grants from the Carlos III Institute of Health and the European Regional Development Fund (PI13/02277, CP16/00039, DTS16/084, and PI16/01580) and Industry and Health Departments of the Basque Country. |
| Databáze: | OpenAIRE |
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