Long non-coding RNA dysregulation is a frequent event in non-small cell lung carcinoma pathogenesis

Amelia Acha-Sagredo,Michael P A Davies,Chryssanthi Moschandrea,Paschalia Pantazi,Michael W Marcus,Bubaraye Uko,John K Field,Lucille Rainbow,Naiara G Bediaga,Triantafillos Liloglou

doi:10.1038/s41416-020-0742-9

Abstract

BackgroundLong non-coding RNAs compose an important level of epigenetic regulation in normal physiology and disease. Despite the plethora of publications of lncRNAs in human cancer, the landscape is still unclear.MethodsMicroarray analysis in 44 NSCLC paired specimens was followed by qPCR-based validation in 29 (technical) and 38 (independent) tissue pairs. Cross-validation of the selected targets was achieved in 850 NSCLC tumours from TCGA datasets.ResultsTwelve targets were successfully validated by qPCR (upregulated: FEZF1-AS1, LINC01214, LINC00673, PCAT6, NUTM2A-AS1, LINC01929; downregulated: PCAT19, FENDRR, SVIL-AS1, LANCL1-AS1, ADAMTS9-AS2 and LINC00968). All of them were successfully cross validated in the TCGA datasets. Abnormal DNA methylation was observed in the promoters of FENDRR, FEZF1-AS1 and SVIL-AS1. FEZF1-AS1 and LINC01929 were associated with survival in the TCGA set.ConclusionsOur study provides through multiple levels of internal and external validation, a comprehensive list of dysregulated lncRNAs in NSCLC. We therefore envisage this dataset to serve as an important source for the lung cancer research community assisting future investigations on the involvement of lncRNAs in the pathogenesis of the disease and providing novel biomarkers for diagnosis, prognosis and therapeutic stratification.

Highlights

Long non-coding RNAs compose an important level of epigenetic regulation in normal physiology and disease
Discovery of aberrant Long non-coding RNAs (lncRNAs) expression profiles in NSCLC On the Gencode v15 microarray, each of the 17,535 randomly selected protein coding and 22,001 lncRNA transcripts is targeted by two probes
An initial comparison between the lncRNA expression profiles of NSCLC tissue and adjacent normal tissue using unsupervised hierarchical clustering analysis showed that samples could be neatly classified based on the expression levels of antisense and lincRNAs

Summary

Introduction

Long non-coding RNAs compose an important level of epigenetic regulation in normal physiology and disease. CONCLUSIONS: Our study provides through multiple levels of internal and external validation, a comprehensive list of dysregulated lncRNAs in NSCLC. We envisage this dataset to serve as an important source for the lung cancer research community assisting future investigations on the involvement of lncRNAs in the pathogenesis of the disease and providing novel biomarkers for diagnosis, prognosis and therapeutic stratification. Long non-coding RNAs (lncRNAs) comprise a heterogeneous group of transcripts >200 nucleotides with no protein coding capacity. LncRNAs show lower expression levels, significantly shorter transcript half-lives and higher cell and tissue specificity than mRNAs.[1,6,7]

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