دورية أكاديمية
Comprehensive functional profiling of long non-coding RNAs through a novel pan-cancer integration approach and modular analysis of their protein-coding gene association networks
| العنوان: | Comprehensive functional profiling of long non-coding RNAs through a novel pan-cancer integration approach and modular analysis of their protein-coding gene association networks |
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| المؤلفون: | Kevin Walters, Radmir Sarsenov, Wen Siong Too, Roseanna K. Hare, Ian C. Paterson, Daniel W. Lambert, Stephen Brown, James R. Bradford |
| المصدر: | BMC Genomics, Vol 20, Iss 1, Pp 1-15 (2019) |
| بيانات النشر: | BMC, 2019. |
| سنة النشر: | 2019 |
| المجموعة: | LCC:Biotechnology LCC:Genetics |
| مصطلحات موضوعية: | lncRNA, Functional profiling, Genes networks, Cancer, Epithelial-mesenchymal transition, Extracellular matrix, Biotechnology, TP248.13-248.65, Genetics, QH426-470 |
| الوصف: | Abstract Background Long non-coding RNAs (lncRNAs) are emerging as crucial regulators of cellular processes in diseases such as cancer, although the functions of most remain poorly understood. To address this, here we apply a novel strategy to integrate gene expression profiles across 32 cancer types, and cluster human lncRNAs based on their pan-cancer protein-coding gene associations. By doing so, we derive 16 lncRNA modules whose unique properties allow simultaneous inference of function, disease specificity and regulation for over 800 lncRNAs. Results Remarkably, modules could be grouped into just four functional themes: transcription regulation, immunological, extracellular, and neurological, with module generation frequently driven by lncRNA tissue specificity. Notably, three modules associated with the extracellular matrix represented potential networks of lncRNAs regulating key events in tumour progression. These included a tumour-specific signature of 33 lncRNAs that may play a role in inducing epithelial-mesenchymal transition through modulation of TGFβ signalling, and two stromal-specific modules comprising 26 lncRNAs linked to a tumour suppressive microenvironment and 12 lncRNAs related to cancer-associated fibroblasts. One member of the 12-lncRNA signature was experimentally supported by siRNA knockdown, which resulted in attenuated differentiation of quiescent fibroblasts to a cancer-associated phenotype. Conclusions Overall, the study provides a unique pan-cancer perspective on the lncRNA functional landscape, acting as a global source of novel hypotheses on lncRNA contribution to tumour progression. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1471-2164 |
| العلاقة: | http://link.springer.com/article/10.1186/s12864-019-5850-7Test; https://doaj.org/toc/1471-2164Test |
| DOI: | 10.1186/s12864-019-5850-7 |
| الوصول الحر: | https://doaj.org/article/6567de301cf0449dafc9b136419e6185Test |
| رقم الانضمام: | edsdoj.6567de301cf0449dafc9b136419e6185 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14712164 |
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| DOI: | 10.1186/s12864-019-5850-7 |