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

Walters, Kevin and Sarsenov, Radmir and Too, Wen Siong and Hare, Roseanna K. and Paterson, Ian Charles and Lambert, Daniel W. and Brown, Stephen and Bradford, James R. (2019) 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. BMC Genomics, 20 (1). p. 454. ISSN 1471-2164

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Official URL: https://doi.org/10.1186/s12864-019-5850-7

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. © 2019 The Author(s).

Item Type: Article
Uncontrolled Keywords: Cancer; Epithelial-mesenchymal transition; Extracellular matrix; Functional profiling; Genes networks; lncRNA; Tumour microenvironment
Subjects: R Medicine
R Medicine > RC Internal medicine
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions: Faculty of Dentistry > Dept of Oral Biology
Depositing User: Mr Ahmad Azwan Azman
Date Deposited: 12 Mar 2020 00:26
Last Modified: 12 Mar 2020 00:26
URI: http://eprints.um.edu.my/id/eprint/23891

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