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.
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.
Shangwei
S
Ning
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.
Yue
Y
Gao
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.
Peng
P
Wang
National Center for Nanoscience and Technology, Beijing, 100190, China.
Xiang
X
Li
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.
Hui
H
Zhi
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.
Yan
Y
Zhang
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.
Yue
Y
Liu
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.
Jizhou
J
Zhang
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.
Maoni
M
Guo
National Center for Nanoscience and Technology, Beijing, 100190, China.
Dong
D
Han
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.
Xia
X
Li
D014408:Biomarkers, Tumor / Q000235:genetics*; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks / Q000235:genetics; D006801:Humans; D053208:Kaplan-Meier Estimate; D035683:MicroRNAs / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D059467:Transcriptome
D014408:Biomarkers, Tumor; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D014157:Transcription Factors
feed-forward loop; long non-coding RNA; network motif; prognostic biomarker; topological feature