Inferring and analyzing module-specific lncRNA-mRNA causal regulatory networks in human cancer

Abstract

It is known that noncoding RNAs (ncRNAs) cover ∼98% of the transcriptome, but do not encode proteins. Among ncRNAs, long noncoding RNAs (lncRNAs) are a large and diverse class of RNA molecules, and are thought to be a gold mine of potential oncogenes, anti-oncogenes and new biomarkers. Although only a minority of lncRNAs is functionally characterized, it is clear that they are important regulators to modulate gene expression and involve in many biological functions. To reveal the functions and regulatory mechanisms of lncRNAs, it is vital to understand how lncRNAs regulate their target genes for implementing specific biological functions. In this article, we review the computational methods for inferring lncRNA-mRNA interactions and the third-party databases of storing lncRNA-mRNA regulatory relationships. We have found that the existing methods are based on statistical correlations between the gene expression levels of lncRNAs and mRNAs, and may not reveal gene regulatory relationships which are causal relationships. Moreover, these methods do not consider the modularity of lncRNA-mRNA regulatory networks, and thus, the networks identified are not module-specific. To address the above two issues, we propose a novel method, MSLCRN, to infer and analyze module-specific lncRNA-mRNA causal regulatory networks. We have applied it into glioblastoma multiforme, lung squamous cell carcinoma, ovarian cancer and prostate cancer, respectively. The experimental results show that MSLCRN, as an expression-based method, could be a useful complementary method to study lncRNA regulations.

Keywords: human cancer; lncRNA; lncRNA–mRNA causal relationship; lncRNA–mRNA co-expression; lncRNA–mRNA interaction; mRNA.