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Non-coding RNA networks in cancer.

ABSTRACT: Thousands of unique non-coding RNA (ncRNA) sequences exist within cells. Work from the past decade has altered our perception of ncRNAs from 'junk' transcriptional products to functional regulatory molecules that mediate cellular processes including chromatin remodelling, transcription, post-transcriptional modifications and signal transduction. The networks in which ncRNAs engage can influence numerous molecular targets to drive specific cell biological responses and fates. Consequently, ncRNAs act as key regulators of physiological programmes in developmental and disease contexts. Particularly relevant in cancer, ncRNAs have been identified as oncogenic drivers and tumour suppressors in every major cancer type. Thus, a deeper understanding of the complex networks of interactions that ncRNAs coordinate would provide a unique opportunity to design better therapeutic interventions.

SUBMITTER: Anastasiadou E

PROVIDER: S-EPMC6337726 | biostudies-other | 2018 Jan

REPOSITORIES: biostudies-other

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Non-coding RNA networks in cancer.

Anastasiadou Eleni E Jacob Leni S LS Slack Frank J FJ

Nature reviews. Cancer 20171124 1

Thousands of unique non-coding RNA (ncRNA) sequences exist within cells. Work from the past decade has altered our perception of ncRNAs from 'junk' transcriptional products to functional regulatory molecules that mediate cellular processes including chromatin remodelling, transcription, post-transcriptional modifications and signal transduction. The networks in which ncRNAs engage can influence numerous molecular targets to drive specific cell biological responses and fates. Consequently, ncRNAs ...[more]

PMID: 29170536

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Project description:BackgroundIncreasing amount of long non-coding RNAs (lncRNAs) have been found involving in many biological processes and played salient roles in cancers. However, up until recently, functions of most lncRNAs in lung cancer have not been fully discovered, particularly in the co-regulated lncRNAs. Thus, this study aims to investigate roles of lncRNA modules and uncover a module-based biomarker in lung adenocarcinoma (LUAD).ResultsWe used gene expression profiles from The Cancer Genome Atlas (TCGA) to construct the lncRNA association networks, from which the highly-associated lncRNAs are connected as modules. It was found that the expression of some modules is significantly associated with patient's survival, including module N1 (HR = 0.62, 95% CI = 0.46-0.84, p = 0.00189); N2 (HR = 0.68, CI = 0.50-0.93, p = 0.00159); N4 (HR = 0.70, CI = 0.52-0.95, p = 0.0205) and P3 (HR = 0.68, CI = 0.50-0.92, p = 0.0123). The lncRNA signature consisting of these four prognosis-related modules, a 4-modular lncRNA signature, is associated with favourable prognosis in TCGA-LUAD (HR = 0.51, CI = 0.37-0.69, p value = 2.00e-05). Afterwards, to assess the performance of the generic modular signature as a prognostic biomarker, we computed the time-dependent area under the receiver operating characteristics (AUC) of this 4-modular lncRNA signature, which showed AUC equals 68.44% on 336th day. In terms of biological functions, these modules are correlated with several cancer hallmarks and pathways, including Myc targets, E2F targets, cell cycle, inflammation/immunity-related pathways, androgen/oestrogen response, KRAS signalling, DNA repair and epithelial-mesenchymal transition (EMT).ConclusionTaken together, we identified four novel LUAD prognosis-related lncRNA modules, and assessed the performance of the 4-modular lncRNA signature being a prognostic biomarker. Functionally speaking, these modules involve in oncogenic hallmarks as well as pathways. The results unveiled the co-regulated lncRNAs in LUAD and may provide a framework for further lncRNA studies in lung cancer.

Dataset Information

Non-coding RNA networks in cancer.

Publications

Non-coding RNA networks in cancer.

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