Abstract
Circular RNA (CircRNA) plays an important role in tumorigenesis and progression of non-small cell lung cancer (NSCLC), but the pathogenesis of NSCLC caused by circRNA has not been fully elucidated. This study aimed to investigate differentially expressed circRNAs and identify the underlying pathogenesis hub genes of NSCLC by comprehensive bioinformatics analysis. Data of gene expression microarrays (GSE101586, GSE101684, and GSE112214) were downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed circRNAs (DECs) were obtained by the “limma” package of R programs and the overlapping operation was implemented of DECs. CircBase database and Cancer-Specific CircRNA database (CSCD) were used to find miRNAs binding to DECs. Target genes of the found miRNAs were identified utilizing Perl programs based on miRDB, miRTarBase, and TargetScan databases. Functional and enrichment analyses of selected target genes were performing using the “cluster profiler” package. Protein-protein interaction (PPI) network was constructed by the Search Tool for the STRING database and module analysis of selected hub genes was performed by Cytoscape 3.7.1. Survival analysis of hub genes were performed by Gene Expression Profiling Interactive Analysis (GEPIA). Respectively, 1 DEC, 249 DECs, and 101 DECs were identified in GSE101586, GSE101684, and GSE112214. A total of eight overlapped circRNAs, 43 miRNAs and 427 target genes were identified. Gene Ontology (GO) enrichment analysis showed these target genes were enriched in biological processes of regulation of histone methylation, Ras protein signal transduction and covalent chromatin modification etc. Pathway enrichment analysis showed these target genes are mainly involved in AMPK signaling pathway, signaling pathways regulating pluripotency of stem cells and insulin signaling pathway etc. A PPI network was constructed based on 427 target genes of the 43 miRNAs. Ten hub genes were found, of which the expression of MYLIP, GAN, and CDC27 were significantly related to NSCLC patient prognosis. Our study provide a deeper understanding the circRNAs-miRNAs-target genes by bioinformatics analysis, which may provide novel insights for unraveling pathogenesis of NSCLC. MYLIP, GAN, and CDC27 genes might serve as novel biomarker for precise treatment and prognosis of NSCLC in the future.
Highlights
Lung cancer has become one of the most serious malignant tumors in the world
Data from each microarray of non-small cell lung cancer (NSCLC) and adjacent normal mucosa tissues were separately analyzed by R program to screen differentially expressed circRNAs
Differentially expressed circRNAs (DECs) were classified and circRNA expression level were evaluated of different samples by pheatmap
Summary
Lung cancer has become one of the most serious malignant tumors in the world. The incidence rate of lung cancer ranks first among men and women in second place (Hu et al, 2018). NSCLC accounts for approximately 85% and about 75% of NSCLC patients were in the advanced stage when they were discovered. Despite new developments for NSCLC in diagnosis and treatment, the overall survival rate remains poor and patients with advanced or metastatic have a worse prognosis (Cheung and Juan, 2017). Chemotherapy and biological targeted therapy are the best ways for the advanced stage patients of NSCLC. The identification of effective biomarkers or therapeutic targets of NSCLC is of great significance in reducing mortality and improving clinical prognosis (Hong et al, 2015)
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