Investigation of key miRNAs and potential mechanisms in non-small cell lung cancer development from chronic obstructive pulmonary disease

Abstract

Lung cancer (LC) is the prominent cause of cancer-related death worldwide, and non-small cell lung cancer (NSCLC) represents approximately 85% of all diagnosed LC cases. It is stated that LC and chronic obstructive pulmonary disease (COPD) are directly linked at a molecular genetics level. Early diagnosis of LC is important for individuals affected by COPD. This study aims to construct a molecular network to discover molecules in NSCLC development from COPD. We downloaded the expression profiles of COPD patients from Gene Expression Omnibus database. The Database Annotation for Visualization and Integrated Discovery tool was utilized for enrichment analysis; STRING and Cytoscape were used for network construction. 15 hub genes were detected among 1517 differentially expressed genes (DEGs). Additionally, 20 differentially expressed miRNAswere identified from five datasets. We constructed miRNA-mRNA regulatory network between the groups of overlapping predicted target genes/DEGs and miRNAs that contained miRNA-mRNA pairs. UALCAN and OncomiR web-portals were used to validate hub genes and miRNAs in NSCLC. JUN, IL6, CD4 and hsa-miR-497-5p, hsa-miR-130b-5p were verified in both lung adenocarcinomas and lung squamous cell carcinomas. This study presents potential biomarkers and mechanisms underlying NSCLC development from COPD that would be targeted for early intervention.