Recent theoretical and experimental studies indicate that long-chain noncoding RNAs (lncRNAs) are essential for the growth and differentiation of cells and the occurrence and development of tumors in epigenetics, but the regulation of lncRNA on gene expression, transcriptional activation, and transcriptional interference in diseases is still unclear. There is an urgent need for effective methods to discover significant lncRNAs with their functions on gene regulatory mechanisms. For this purpose, a new method of extracting significant lncRNA based on pathway crosstalk and dysfunction caused by the differentially expressed genes in lung adenocarcinoma (LUAD) was proposed. The pathway analysis method based on global influence (PAGI) was first applied to find the feature genes that play an important role in the crosstalks of disease-related pathways. Then to explore the hub lncRNAs, the weighted gene coexpression network analysis (WGCNA) was used to construct coexpression models of the feature genes and lncRNAs. The experiment results showed that 64 out of the 322 hub lncRNAs were closely related to the clinical features of patients with LUAD. Among them, nine lncRNAs (UCA1, LINC00857, PVT1, PCAT6, LINC00460, LINC00319, AP000553.1, AP000439.2, and AP005233.2) were identified to be tightly correlated with non-small-cell lung cancer (NSCLC) pathways. In summary, we offer an effective way to extract significant lncRNA by dysfunctional pathway crosstalk in LUAD which allows the selected lncRNAs with more biologically interpreted and reproducible results. This method can be applied to other diseases and provide useful information for understanding the pathogenesis of human cancer.
Keywords: long-chain noncoding RNAs (lncRNAs); lung adenocarcinoma (LUAD); pathway analysis method based on global influence (PAGI); pathway crosstalk; weighted gene coexpression network analysis (WGCNA).
© 2018 Wiley Periodicals, Inc.