Abstract

BackgroundAccumulating evidence indicates that long non-coding RNAs (lncRNAs) are involving in the tumorigenesis and metastasis of lung cancer. The aim of the study is to systematically characterize the lncRNA-associated competing endogenous RNA (ceRNA) network and identify key lncRNAs in the development of stage I lung adenocarcinoma (LUAD).MethodsTotally, 1,955 DEmRNAs, 165 DEmiRNAs and 1,107 DElncRNAs were obtained in 10 paired normal and LUAD tissues. And a total of 8,912 paired lncRNA-miRNA-mRNA network was constructed. Using the Cancer Genome Atlas (TCGA) dataset, the module of ME turquoise was revealed to be most relevant to the progression of LUAD though Weighted Gene Co-expression Network Analysis (WGCNA).ResultsOf the lncRNAs identified, LINC00639, RP4-676L2.1 and FENDRR were in ceRNA network established by our RNA-sequencing dataset. Using univariate Cox regression analysis, FENDRR was a risk factor of progression free survival (PFS) of stage I LUAD patients (HRs = 1.69, 95%CI 1.07–2.68, P < .050). Subsequently, diffe rential expression of FENDRR in paired normal and LUAD tissues was detected significant by real-time quantitative (qRT-PCR) (P < 0.001).ConclusionsThis study, for the first time, deciphered the regulatory role of FENDRR/miR-6815-5p axis in the progression of early-stage LUAD, which is needed to be established in vitro and in vivo.

Highlights

  • Lung cancer remains the prominent contributor of cancer-related mortality, with the worldwide 5-year survival rate of which is around 16.6% [1, 2]

  • The heatmaps of DEmRNAs, DEmiRNAs and DElncRNAs were presented in Fig. 2AC, and the top 20 of which were displayed in Table S1, 2, 3, respectively

  • To explore the significance of DElncRNAs that might involve in lung adenocarcinoma (LUAD), we performed functional enrichment analysis of target mRNAs

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Summary

Introduction

Lung cancer remains the prominent contributor of cancer-related mortality, with the worldwide 5-year survival rate of which is around 16.6% [1, 2]. Accumulating evidences revealed that lncRNA could disrupt miRNA-mediated degradation of target mRNAs by acting as “miRNA sponges” [13], indicating coding and noncoding RNAs could control one another through their ability to compete for miRNA binding locus, which termed as “ceRNA”. Under this hypothesis, a growing number of evidence revealed that ceRNA axis could contribute to tumorigenesis, progression and metastasis of cancer [14, 15]. The aim of the study is to systematically characterize the lncRNA-associated competing endogenous RNA (ceRNA) network and identify key lncRNAs in the development of stage I lung adenocarcinoma (LUAD)

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