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Nucleic Acids Res. 2015 Apr 20;43(7):3478-89. doi: 10.1093/nar/gkv233. Epub 2015 Mar 23.

Identification of lncRNA-associated competing triplets reveals global patterns and prognostic markers for cancer.

Author information

1
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
2
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China guoz@ems.hrbmu.edu.cn.
3
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China lixia@hrbmu.edu.cn.

Abstract

Recent studies have suggested that long non-coding RNAs (lncRNAs) can interact with microRNAs (miRNAs) and indirectly regulate miRNA targets though competing interactions. However, the molecular mechanisms underlying these interactions are still largely unknown. In this study, these lncRNA-miRNA-gene interactions were defined as lncRNA-associated competing triplets (LncACTs), and an integrated pipeline was developed to identify lncACTs that are active in cancer. Competing lncRNAs had sponge features distinct from non-competing lncRNAs. In the lncACT cross-talk network, disease-associated lncRNAs, miRNAs and coding-genes showed specific topological patterns indicative of their competence and control of communication within the network. The construction of global competing activity profiles revealed that lncACTs had high activity specific to cancers. Analyses of clustered lncACTs revealed that they were enriched in various cancer-related biological processes. Based on the global cross-talk network and cluster analyses, nine cancer-specific sub-networks were constructed. H19- and BRCA1/2-associated lncACTs were able to discriminate between two groups of patients with different clinical outcomes. Disease-associated lncACTs also showed variable competing patterns across normal and cancer patient samples. In summary, this study uncovered and systematically characterized global properties of human lncACTs that may have prognostic value for predicting clinical outcome in cancer patients.

PMID:
25800746
PMCID:
PMC4402541
DOI:
10.1093/nar/gkv233
[Indexed for MEDLINE]
Free PMC Article

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