Construction of a metastasis-associated ceRNA network reveals a prognostic signature in lung cancer

Shuzhen Liu,Guoyan An,Lei Lei,Bianbian Yan,Qing Cao,Zewen Dong

doi:10.1186/s12935-020-01295-8

Abstract

BackgroundLung cancer is the most common cancer worldwide, and metastasis is the leading cause of lung cancer related death. However, the molecular network involved in lung cancer metastasis remains incompletely described. Here, we aimed to construct a metastasis-associated ceRNA network and identify a lncRNA prognostic signature in lung cancer.MethodsRNA expression profiles were downloaded from The Cancer Genome Atlas (TCGA) database. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses and gene set enrichment analysis (GSEA) were performed to investigate the function of these genes. Using Cox regression analysis, we found that a 6 lncRNA signature may serve as a candidate prognostic factor in lung cancer. Finally, we used Transwell assays with lung cancer cell lines to verify that LINC01010 acts as a tumor suppressor.ResultsWe identified 1249 differentially expressed (DE) mRNAs, 440 DE lncRNAs and 26 DE miRNAs between nonmetastatic and metastatic lung cancer tissues. GO and KEGG analyses confirmed that the identified DE mRNAs are involved in lung cancer metastasis. Using bioinformatics tools, we constructed a metastasis-associated ceRNA network for lung cancer that includes 117 mRNAs, 23 lncRNAs and 22 miRNAs. We then identified a 6 lncRNA signature (LINC01287, SNAP25-AS1, LINC00470, AC104809.2, LINC00645 and LINC01010) that had the greatest prognostic value for lung cancer. Furthermore, we found that suppression of LINC01010 promoted lung cancer cell migration and invasion.ConclusionsThis study might provide insight into the identification of potential lncRNA biomarkers for diagnosis and prognosis in lung cancer.

Highlights

Lung cancer is the most common cancer worldwide, and metastasis is the leading cause of lung cancer related death
This study reveals a Competing endogenous RNAs (ceRNAs) network in metastatic lung cancer, which may provide a useful basis for formulating early diagnosis and individualized treatments
With the criteria of |logFC| > 1 and False discovery rate (FDR) < 0.05, we identified 1249 differentially expressed (DE) Messenger RNA (mRNA) (569 upregulated and 680 downregulated), 440 DE Long non-coding RNA (lncRNA) (221 upregulated and 219 downregulated) and 26 miRNAs (21 up-regulated and 5 downregulated) between nonmetastatic and metastatic tumor tissues

Summary

Introduction

Lung cancer is the most common cancer worldwide, and metastasis is the leading cause of lung cancer related death. We aimed to construct a metastasis-associated ceRNA network and identify a lncRNA prognostic signature in lung cancer. Lung cancer is the most common cancer worldwide and the leading cause of cancer-related death in men and the second in women [1, 2]. Increasing studies have revealed that lncRNAs. Cao et al Cancer Cell Int (2020) 20:208 are involved in many cellular processes, such as myocyte differentiation, immune response, cancer cell metastasis, proliferation, and drug resistance [10,11,12]. Overexpression of lncRNA HAND2-AS1 inhibited migration of non-small cell lung cancer cells by downregulating TGF-β1 [13]. Fang et al reported that lncRNA HOTAIR affects chemoresistance by regulating HOXA1 methylation in small cell lung cancer [14]

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