دورية أكاديمية
Tumour mutations in long noncoding RNAs enhance cell fitness
| العنوان: | Tumour mutations in long noncoding RNAs enhance cell fitness |
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| المؤلفون: | Roberta Esposito, Andrés Lanzós, Tina Uroda, Sunandini Ramnarayanan, Isabel Büchi, Taisia Polidori, Hugo Guillen-Ramirez, Ante Mihaljevic, Bernard Mefi Merlin, Lia Mela, Eugenio Zoni, Lusine Hovhannisyan, Finn McCluggage, Matúš Medo, Giulia Basile, Dominik F. Meise, Sandra Zwyssig, Corina Wenger, Kyriakos Schwarz, Adrienne Vancura, Núria Bosch-Guiteras, Álvaro Andrades, Ai Ming Tham, Michaela Roemmele, Pedro P. Medina, Adrian F. Ochsenbein, Carsten Riether, Marianna Kruithof-de Julio, Yitzhak Zimmer, Michaela Medová, Deborah Stroka, Archa Fox, Rory Johnson |
| المصدر: | Nature Communications, Vol 14, Iss 1, Pp 1-21 (2023) |
| بيانات النشر: | Nature Portfolio |
| سنة النشر: | 2023 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | Science |
| 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 |
| اللغة: | English |
| تدمد: | 2041-1723 |
| العلاقة: | https://doi.org/10.1038/s41467-023-39160-7Test; https://doaj.org/toc/2041-1723Test; https://doaj.org/article/ac68b1f51d77424ab680971f8fdf0575Test |
| DOI: | 10.1038/s41467-023-39160-7 |
| الإتاحة: | https://doi.org/10.1038/s41467-023-39160-7Test https://doaj.org/article/ac68b1f51d77424ab680971f8fdf0575Test |
| رقم الانضمام: | edsbas.85118FE8 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 20411723 |
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| DOI: | 10.1038/s41467-023-39160-7 |