Academic Journal
Tumour mutations in long noncoding RNAs enhance cell fitness.
| العنوان: | Tumour mutations in long noncoding RNAs enhance cell fitness. |
|---|---|
| المؤلفون: | Esposito, Roberta, Lanzós, Andrés, Uroda, Tina, Ramnarayanan, Sunandini, Büchi, Isabel, Polidori, Taisia, Guillen-Ramirez, Hugo, Mihaljevic, Ante, Merlin, Bernard Mefi, Lia, Mela, Zoni, Eugenio, Hovhannisyan, Lusine, McCluggage, Finn, Medo, Matúš, Basile, Giulia, Meise, Dominik F, Zwyssig, Sandra, Wenger, Corina, Schwarz, Kyriakos, Vancura, Adrienne, Bosch-Guiteras, Núria, Andrades, Álvaro, Tham, Ai Ming, Roemmele, Michaela, Ochsenbein, Adrian, Riether, Carsten, Kruithof-de Julio, Marianna, Zimmer, Yitzhak, Medova, Michaela, Stroka, Deborah, Fox, Archa, Johnson, Rory |
| المصدر: | Esposito, Roberta; Lanzós, Andrés; Uroda, Tina; Ramnarayanan, Sunandini; Büchi, Isabel; Polidori, Taisia; Guillen-Ramirez, Hugo; Mihaljevic, Ante; Merlin, Bernard Mefi; Lia, Mela; Zoni, Eugenio; Hovhannisyan, Lusine; McCluggage, Finn; Medo, Matúš; Basile, Giulia; Meise, Dominik F; Zwyssig, Sandra; Wenger, Corina; Schwarz, Kyriakos; Vancura, Adrienne; . (2023). Tumour mutations in long noncoding RNAs enhance cell fitness. Nature communications, 14(1), p. 3342. Nature Publishing Group 10.1038/s41467-023-39160-7 |
| بيانات النشر: | Nature Publishing Group |
| سنة النشر: | 2023 |
| المجموعة: | BORIS (Bern Open Repository and Information System, University of Bern) |
| مصطلحات موضوعية: | 610 Medicine & health |
| الوصف: | Long noncoding RNAs (lncRNAs) are linked to cancer via pathogenic changes in their expression levels. Yet, it remains unclear whether lncRNAs can also impact tumour cell fitness via function-altering somatic "driver" mutations. To search for such driver-lncRNAs, we here perform a genome-wide analysis of fitness-altering single nucleotide variants (SNVs) across a cohort of 2583 primary and 3527 metastatic tumours. The resulting 54 mutated and positively-selected lncRNAs are significantly enriched for previously-reported cancer genes and a range of clinical and genomic features. A number of these lncRNAs promote tumour cell proliferation when overexpressed in in vitro models. Our results also highlight a dense SNV hotspot in the widely-studied NEAT1 oncogene. To directly evaluate the functional significance of NEAT1 SNVs, we use in cellulo mutagenesis to introduce tumour-like mutations in the gene and observe a significant and reproducible increase in cell fitness, both in vitro and in a mouse model. Mechanistic studies reveal that SNVs remodel the NEAT1 ribonucleoprotein and boost subnuclear paraspeckles. In summary, this work demonstrates the utility of driver analysis for mapping cancer-promoting lncRNAs, and provides experimental evidence that somatic mutations can act through lncRNAs to enhance pathological cancer cell fitness. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| Relation: | https://boris.unibe.ch/183272/ |
| الاتاحة: | https://boris.unibe.ch/183272/1/s41467-023-39160-7.pdf https://boris.unibe.ch/183272/ |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.6DD85516 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |