Abstract
Long non-coding RNAs (lncRNAs), transcription factors and microRNAs can form lncRNA-mediated feed-forward loops (L-FFLs), which are functional network motifs that regulate a wide range of biological processes, such as development and carcinogenesis. However, L-FFL network motifs have not been systematically identified, and their roles in human cancers are largely unknown. In this study, we computationally integrated data from multiple sources to construct a global L-FFL network for six types of human cancer and characterized the topological features of the network. Our approach revealed several dysregulated L-FFL motifs common across different cancers or specific to particular cancers. We also found that L-FFL motifs can take part in other types of regulatory networks, such as mRNA-mediated FFLs and ceRNA networks, and form the more complex networks in human cancers. In addition, survival analyses further indicated that L-FFL motifs could potentially serve as prognostic biomarkers. Collectively, this study elucidated the roles of L-FFL motifs in human cancers, which could be beneficial for understanding cancer pathogenesis and treatment.
Highlights
Long non-coding RNAs [1] are pervasive across the genome [2, 3] and dysregulation of their expression is associated with many human diseases [4, 5], including cancer [6]
We found that the Long non-coding RNAs (lncRNAs) IQCH-AS1 interacts with E2F1 and miR-15b, suggesting it might be implicated in cancer regulation through the lncRNA-mediated feed-forward loops (L-FFLs) network
We focused on a novel network motif, the L-FFL motif, and developed a computational approach to study it by integrating interaction and expression data of lncRNA, mRNAs and miRNAs
Summary
Long non-coding RNAs (lncRNAs, > 200 nucleotides in length) [1] are pervasive across the genome [2, 3] and dysregulation of their expression is associated with many human diseases [4, 5], including cancer [6]. The expression of lncRNA is regulated at the transcriptional level by transcription factors (TFs) [7] and at the post-transcriptional level by microRNAs (miRNAs) [8,9,10], leading to differential expression in different development and disease statuses. While both TFs and miRNAs regulate lncRNAs, TFs regulate miRNAs [7]. There has been no large-scale attempt to identify L-FFL network motifs and their specific roles in human cancers
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