Dataset Information

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

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.

SUBMITTER: Ning S

PROVIDER: S-EPMC5216772 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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

Ning Shangwei S Gao Yue Y Wang Peng P Li Xiang X Zhi Hui H Zhang Yan Y Liu Yue Y Zhang Jizhou J Guo Maoni M Han Dong D Li Xia X

Oncotarget 20160701 29

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 ...[more]

PMID: 27322142

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Project description:Ischemic stroke (IS) accounts for the leading cause of disability and mortality in China. Increasing researchers are studying the effects of neuroprotective agents on IS. However, the molecular mechanisms of feed-forward loops (FFLs) associated with neuroprotection in the pathogenesis of IS need to be further studied. A protein-protein interaction (PPI) network of IS immune genes was constructed to decipher the characters and excavate 3 hub genes (PI3K, IL6, and TNF) of immunity. Then, we identified two hub clusters of IS immune genes, and the cytokine-cytokine receptor interaction pathway was discovered on the pathway enrichment results of both clusters. Combined with GO enrichment analysis, the cytokines participate in the inflammatory response in the extracellular space of IS patients. Next, a transcription factor (TF)-miRNA-immune gene network (TMIGN) was established by extracting four regulatory pairs (TF-miRNA, TF-gene, miRNA-gene, and miRNA-TF). Then, we detected 3-node regulatory motif types in the TMIGN network. According to the criteria we set for defining 3-node motifs, the motif with the highest Z-score (3-node composite FFL) was picked as the statistically evident motif, which was merged to construct an immune-associated composite FFL motif-specific sub-network (IA-CFMSN), which contained 21 3-node FFLs composed of 13 miRNAs, 4 TFs, 9 immune genes, and 1 TF& immune gene, among which TP53 and VEGFA were prominent TF and immune gene, respectively. In addition, the immune genes in IA-CFMSN were used for identifying associated pathways and drugs to further clarify the immune regulation mechanism and neuroprotection after IS. As a result, 5 immune genes targeted by 20 drugs were identified and the Angiotensin II Receptor Blockers (ARBs) target AGTR1 was found to be a neuroprotective drug for IS. In the present study, the construction of IA-CFMSN provides IS immune-associated FFLs for further experimental studies, providing new prospects for the discovery of new biomarkers and potential drugs for IS.

Dataset Information

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

Publications

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

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