Identification of lncRNA-miRNA-mRNA ceRNA network as biomarkers for lung adenocarcinoma

Lung cancer (LC) is one of the most common cancers worldwide, with the highest rate of mortality and morbidity in both genders. It is classified into two main types: small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC). NSCLC is subdivided into several histological subtypes including adenocarcinoma (LUAD), adenosquamous carcinoma, squamous cell carcinoma (LUSC), and large cell carcinoma (LCC). LUAD is a common subtype of LC which accounts for approximately ۴۰% of all LC. Despite the emergence of promising new therapies, LUAD remains a major public health problem with a ۵-year survival rate of ۱۵% In this study, bioinformatics analyses were done to identify a potential gene family and a ceRNA network including a novel miRNA, mRNA, and lncRNA which any changes in their expression may effect on the Pancreatic tumor growth. Method: A gene expression profile of Lung adenocarcinoma (GSE۸۵۸۴۱) was obtained from gene expression omnibus (GEO), a transcriptional and expression data repository. Normalization of data was implemented with the GEO۲R to find differentially expressed genes (DEGs) in tumor tissue samples compared to normal tissue samples. A threshold value of fold change >۲ or ۲ < and p-value <۰.۰۵ were chosen to determine DEGs. Following DEG identification, gene ontology (GO) term, and pathway enrichment analysis were performed utilizing Enrichr. IGF۲BP۳ was chosen as an up-regulated gene (FC=۲.۶۴, adj p-v=۴.۲۹E-۰۴). Reactome was deployed to analyze the pathway enrichment of IGF۲BP۳. To discover the connection between the other genes and IGF۲BP۳ which are involved in the Insulin-like Growth Factor-۲ mRNA Binding Proteins (IGF۲BPs) pathway a protein-protein interaction (PPI) network was reconstructed utilizing STRING. Cytoscape v۳.۱۰.۲ was used for network visualization and analysis. Gene expression profiling interactive analysis (GEPIA۲) was employed to validate the selected gene to investigate its potential to be chosen as a biomarker. thus, in patients with Lung adenocarcinoma overall survival (OS) and box plot related to hub gene were examined. miRWALK database was used to find a novel miRNA and by using the ENCORI database the ceRNA network between the selected mRNA, miRNA, and a LncRNA was found. Result: In tumor samples, IGF۲BP۳ was found as a significantly up-regulated gene (logFC=۲.۶۴). The survival analysis revealed a strong correlation between lung adenocarcinoma (LUAD) and IGF۲BP۳ overexpression. According to REACTOM, this gene was directly involved in the Insulin-like Growth Factor mRNA Binding Factor-۳ pathway. hsa-miR-۶۷۰-۵p was identified by mRNA-miRNA interactions analysis as a significant and novel microRNA with a suppressor role in the ۳'UTR region of our gene. This result was confirmed by correlation analysis between hsa-miR-۶۷۰-۵p and IGF۲BP۳ (adj.P.Val = ۴.۲۹E-۰۴). The overall survival analysis of hsa-miR-۶۷۰-۵p in LUAD was also significant (log-rank P= ۰.۰۷). In contrast, RNF۲۱۶P۱ was discovered as LncRNA for hsa-miR-۶۷۰-۵p to assemble a novel ceRNA network in LUAD. Conclusion: According to the above-mentioned events, the overexpression of the IGF۲BP۳ gene acts as a tumor growth factor. These findings lead us to a precise relationship between hsa-miR-۶۷۰-۵p, RNF۲۱۶P۱, and IGF۲BP۳ which may cause Lung cancer. Ultimately, further experimental analysis is needed to confirm our findings.

کلیدواژه ها:

Biomarker ، Lung adenocarcinoma ، Microarray ، ceRNA network