Tissue-Specific Target Analysis of Disease-Associated MicroRNAs in Human Signaling Pathways

被引:16
作者
Kowarsch, Andreas [1 ]
Marr, Carsten [1 ]
Schmidl, Daniel [1 ,2 ]
Ruepp, Andreas [1 ]
Theis, Fabian J. [1 ,2 ]
机构
[1] Helmholtz Zentrum Munchen, Inst Bioinformat & Syst Biol, Neuherberg, Germany
[2] Tech Univ Munich, Inst Math Sci, D-8046 Garching, Germany
关键词
REL/NF-KAPPA-B; MESSENGER-RNA; C-FOS; CANCER; GENE; IDENTIFICATION; EXPRESSION; GROWTH; CELLS; TRANSCRIPTION;
D O I
10.1371/journal.pone.0011154
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
MicroRNAs are a large class of post-transcriptional regulators that bind to the 39 untranslated region of messenger RNAs. They play a critical role in many cellular processes and have been linked to the control of signal transduction pathways. Recent studies indicate that microRNAs can function as tumor suppressors or even as oncogenes when aberrantly expressed. For more general insights of disease-associated microRNAs, we analyzed their impact on human signaling pathways from two perspectives. On a global scale, we found a core set of signaling pathways with enriched tissue-specific microRNA targets across diseases. The function of these pathways reflects the affinity of microRNAs to regulate cellular processes associated with apoptosis, proliferation or development. Comparing cancer and non-cancer related microRNAs, we found no significant differences between both groups. To unveil the interaction and regulation of microRNAs on signaling pathways locally, we analyzed the cellular location and process type of disease-associated microRNA targets and proteins. While disease-associated proteins are highly enriched in extracellular components of the pathway, microRNA targets are preferentially located in the nucleus. Moreover, targets of disease-associated microRNAs preferentially exhibit an inhibitory effect within the pathways in contrast to disease proteins. Our analysis provides systematic insights into the interaction of disease-associated microRNAs and signaling pathways and uncovers differences in cellular locations and process types of microRNA targets and disease-associated proteins.
引用
收藏
页数:9
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