Integrated Bioinformatics Analysis Deciphering the microRNA Regulation in Protein-Protein Interaction Network in Lung Adenocarcinoma

Abstract

Background: The architecture of the protein-protein interaction (PPI) network in any organism relies on their gene expression signature. microRNAs (miRNAs) have recently emerged as major post transcriptional regulators that control PPI by targeting mainly untranslated regions of the gene encoding proteins. Here, we aimed to unveil the role of miRNAs in the PPI network for identifying potential molecular targets for lung adenocarcinoma (LUAD). Materials and methods: The expression profiles of miRNAs and mRNAs were collected from the NCBI Gene Expression Omnibus (GEO) database (GSE74190 and GSE116959). Abnormally expressed mRNAs from the data were appointed to construct a PPI network and hence incorporated with the miRNA−mRNA regulatory network. The miRNAs and mRNAs in this network were subjected to functional enrichment. Through the network analysis, hubs were identified and their mutation rate and probability of cooccurrence were calculated. Results: We identified 17 miRNAs and 429 mRNAs signature for differentially altered transcriptome in LUAD. The combined miRNA−mRNA regulatory network exhibited scale−free characteristics. Network analysis showed 5 miRNA (including hsa−miR−486−5p, hsa−miR−200b−5p, and hsa−miR−130b−5p) and 10 mRNA (including ASPM, CCNB1, TTN, TPX2, and BIRC5) which expressively contribute in the LUAD. We further investigated the hub genes and noticed that ASPM and TTN had the maximum rate of mutation and possessed a high tendency of cooccurrence in LUAD. Conclusion: This study provides a unique network approach to the exploration of the underlying molecular mechanism in LUAD. Identified mRNAs and miRNAs may therefore, serve as significant prognostic predictors and therapeutic targets.