Journal
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 23, Issue 2, Pages 967-984Publisher
WILEY
DOI: 10.1111/jcmm.13997
Keywords
ceRNAs; differentially expressed genes; subpathways; topological property
Categories
Funding
- National Natural Science Foundation of China [81572341, 61601150]
- National Science Foundation of Heilongjiang Province [JJ2016ZR1232/F2016031]
- Yu Weihan Outstanding Youth Training Fund of Harbin Medical University
- Wu Liande Youth Science Research Fund of Harbin Medical University (Daqing) [DQWLD201703]
- Postdoctoral Researchers in Heilongjiang Scientific Research
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Competing endogenous RNAs (ceRNAs) represent a novel mechanism of gene regulation that may mediate key subpathway regions and contribute to the altered activities of pathways. However, the classical methods used to identify pathways fail to specifically consider ceRNAs within the pathways and key regions impacted by them. We proposed a powerful strategy named ce-Subpathway for the identification of ceRNA-mediated functional subpathways. It provided an effective level of pathway analysis via integrating ceRNAs, differentially expressed (DE) genes and their key regions within the given pathways. We respectively analysed one pulmonary arterial hypertension (PAH) and one myocardial infarction (MI) data sets and demonstrated that ce-Subpathway could identify many subpathways whose corresponding entire pathways were ignored by those non-ceRNA-mediated pathway identification methods. And these pathways have been well reported to be associated with PAH/MI-related cardiovascular diseases. Further evidence showed reliability of ceRNA interactions and robustness/reproducibility of the ce-Subpathway strategy by several data sets of different cancers, including breast cancer, oesophageal cancer and colon cancer. Survival analysis was finally applied to illustrate the clinical application value of the ceRNA-mediated functional subpathways using another data sets of pancreatic cancer. Comprehensive analyses have shown the power of a joint ceRNAs/DE genes and subpathway strategy based on their topologies.
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