期刊
JOURNAL OF DRUG TARGETING
卷 19, 期 5, 页码 354-364出版社
TAYLOR & FRANCIS LTD
DOI: 10.3109/1061186X.2010.504261
关键词
Drug target; microRNA; topological property; protein-protein interaction network
资金
- National Natural Science Foundation of China [30370798, 30571034, 30570424, 30900837, 20060213024]
- National High Tech Development Project of China
- 863 Program [2007AA02Z329]
- National Basic Research Program of China
- 973 Program [2008CB517302]
- National Science Foundation of Heilongjiang Province [ZJG0501, 1055HG009, GB03C602-4, BMFH060044]
- Science Foundation for Post Doctorate Research from the People's Government of Heilongjiang Province [LRB08-393]
- Heilongjiang Provincial Health Department [2009-253]
- New Century Hundred-Thousand-Ten Thousand Talents Project of Beijing City
The investigation of topological properties of proteins in protein-protein interaction network (PPIN) has great potentials to identify basic protein functions and mechanisms of action. Based on human PPIN, previous study has shown that the topological properties of drug targets are significantly distinguished from those of proteins that are not targeted by drugs (non-drug-targets). MicroRNAs (miRNAs) are known to regulate gene expression at the post-transcriptional level. To determine whether the differences in topological properties between drug targets and non-drug-targets are dominated by the proteins that are regulated by miRNA, we divided the drug targets into two sets: those are regulated by miRNA (mir-drug-targets) and those are not regulated by miRNA (non-mir-drug-targets). We compared the probability of interactions and five topological properties among the three types of proteins in human PPIN. Our results demonstrated that mir-drug-targets preferentially interact with other mir-drug-targets and tend to be hub-bottlenecks. However, there was no bias on topological properties between non-mir-drug-targets and non-drug-targets. The same topological features are observed among non-drug targets. These findings indicate that miRNA regulation has an important role in human PPIN, and may be useful in the development of novel drugs.
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