Identification of LncRNA-microRNA-mRNA Network in Non-small Cell Lung Carcinoma through Bioinformatics-Based Tools

Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) are the two most common types of lung cancer, accounting for a significant proportion of lung cancer patients’ worldwide. Competing endogenous RNAs (ceRNAs) network compounds the multiple layers of crosstalk to decipher the interactions between coding and non-coding RNAs. The role of the ceRNA network in regulatory mechanisms involved in cancer development and progression is highlighted by constructing and analyzing these complex networks into the molecular landscape of intricate interplays. By studying the intricate connections of ceRNA networks in LUAD and LUSC, focusing on the expression profiles of both datasets and key various molecules using centrality factors, our investigation contributes to a deeper understanding of the molecular underpinnings of cancer development. Two miRNAs, hsa-miR-۵۶۸۳ and hsa-miR-۳۷۸c explored as the main central nodes, interacting significantly to the targets and highly associated with expression patterns in tumor samples as up-regulated miRNAs. PVT۱, down-regulated lncRNA in both LUAD and LUSC tumor samples, emerged as an overlapped lncRNA between two ceRNA networks interacting with hsa-miR-۳۷۸c. FAM۸۳f gene emerged as a significant overlapped central target in all centrality subgraphs of both ceRNA networks, interacting with hsa-miR-۳۷۸c with high-ranking criteria. To identify the critical impacts of smoking status on expression patterns, we found that the expression of key biomolecules, PVT۱ (lncRNA), miR-۳۷۸C, and FAM۸۳f (mRNA), exhibited that smokers had a greater decrease in PVT۱ and FAM۸۳f expression patterns than non-smokers. Besides, different expression patterns of miR-۳۷۸C based on smoking status exhibited down regulation and up regulation in non-smokers and smokers respectively. PVT۱ was down-regulated in LUAD and LUSC groups, while miR-۳۷۸C and FAM۸۳F expression levels were increased in LUSC samples. There was no significant co-expression between miR-۳۷۸C and FAM۸۳f, but a significant relationship between PVT۱ and FAM۸۳f was observed. Our findings reveal the roles of PVT۱ and miR-۳۷۸c in the ceRNA networks, associated with expression levels and smoking phenotypes.

کلیدواژه ها:

LUAD ، LUSC ، expression profiling ، ceRNA network ، non-coding RNAs