Identification of key differentially expressed miRNAs and their potential target genes in Non-small cell lung cancer using bioinformatics analysis

Background: Non-small cell lung cancer (NSCLC) which is responsible for over ۸۰% of lungcancer cases, is identified by a poor prognosis. Plenty of evidence shows that microRNAs play animportant role in cancerous cell development by targeting a wide range of mRNAs. In this study, weaimed to find the most important miRNAs involved in NSCLC development as well as their targetgenes .Methods: A microarray dataset containing miRNA profiles from the total blood of NSCLC samples andhealthy controls was downloaded from the Gene Expression Omnibus (GEO) database. R software wasused to investigate the alteration of miRNAs expression and identification of their target mRNAs.Moreover, Funrich ۳.۱.۳, functional and pathway enrichment analyses were performed for the selectedtarget genes. Then, the protein-protein interaction (PPI) network and hub-genes were elucidated usingthe STRING database and Cytoscape, separately. Moreover, the interactions between hub genes anddysregulated miRNAs were established .Results: Differentially expressed miRNAs (DEmiRNAs) were identified from GSE۱۷۶۸۱ datasets,among which ۱۳ downregulated and ۱۱ upregulated DEmiRNAs were recognized in NSCLC samples .There were ۲۰۸ potential predicted target genes, which ۱۲۹ genes were targeted by up-regulatedmiRNAs, and ۷۹ were targeted via down-regulated ones. While genes targeted by up-regulated miRNAswere significantly enriched in the FoxO family signaling, down-regulated miRNAs targeted genes werehighly enriched in the TRAIL signaling pathway. ۱۰ pivotal bub genes for down and upregulatedDEmiRNAs were identified in the PPI network among which Myc and HSPa۸ showed the highest nodedegree .Conclusions: This study may provide new perspectives for future studies in the context of NSCLC bysuggesting a list of differentially expressed miRNAs and their potential target genes that may serve asnovel markers in both the diagnosis and treatment of NSCLC patients.

کلیدواژه ها:

Non-small cell lung cancer ، Network analysis ، Hub gene identification ، MicroRNAs ، DemiRs