Construction of a lncRNA-mediated feed-forward loop network reveals global topological features and prognostic motifs in human cancers

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.