Long non-coding RNAs (lncRNAs) have been found to play important roles in various biological processes; however, many of their functions remain unclear. In this study, we present a novel approach to identify the lncRNA-associated protein-protein interaction (PPI) modules and ascertain their functions in human lung squamous cell carcinoma. We collected lncRNA and mRNA expression profiles of lung squamous cell carcinoma from The Cancer Genome Atlas. To identify the lncRNA-associated PPI modules, lncRNA-mRNA co-expression networks were first constructed based on the mutual ranks of expression correlations. Next, we examined whether the co-expressed mRNAs of a specific lncRNA were closely connected by PPIs. For this, a significantly connected mRNA set was considered to be the lncRNA-associated PPI module. Finally, the prospective functions of a lncRNA was inferred using Gene Ontology enrichment analysis on the associated module. We found that lncRNA-associated PPI modules were subtype-dependent and each subtype had unique molecular mechanisms. In addition, antisense lncRNAs and sense genes tended to be functionally associated. Our results might provide new directions for understanding lncRNA regulations in lung cancer. The analysis pipeline was implemented in a web tool, available at http://lncin.ym.edu.tw/.

Supplementary data are available at Bioinformatics online.

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