| Autor: |
Galatenko VV; Lomonosov Moscow State University, Leninskie Gory 1, 119991, Moscow, Russia. vgalat@imscs.msu.ru.; SRC Bioclinicum, Ugreshskaya str. 2/85, 115088, Moscow, Russia. vgalat@imscs.msu.ru.; Tauber Bioinformatics Research Center, University of Haifa, 199 Aba Khoushy Ave., Mount Carmel, 3498838, Haifa, Israel. vgalat@imscs.msu.ru., Galatenko AV; Lomonosov Moscow State University, Leninskie Gory 1, 119991, Moscow, Russia., Samatov TR; SRC Bioclinicum, Ugreshskaya str. 2/85, 115088, Moscow, Russia.; Evotec International GmbH, Marie-Curie Str. 7, 37079, Göttingen, Germany., Turchinovich AA; SciBerg e.Kfm, Birkenauer Str. 7, 68309, Mannheim, Germany., Shkurnikov MY; P. Hertsen Moscow Oncology Research Institute, National Center of Medical Radiological Research, Second Botkinsky lane 3, 125284, Moscow, Russia., Makarova JA; P. Hertsen Moscow Oncology Research Institute, National Center of Medical Radiological Research, Second Botkinsky lane 3, 125284, Moscow, Russia.; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova str. 32, 119991, Moscow, Russia., Tonevitsky AG; SRC Bioclinicum, Ugreshskaya str. 2/85, 115088, Moscow, Russia. tonevitsky@mail.ru.; P. Hertsen Moscow Oncology Research Institute, National Center of Medical Radiological Research, Second Botkinsky lane 3, 125284, Moscow, Russia. tonevitsky@mail.ru. |
| Abstrakt: |
MicroRNAs (miRNAs) are a family of short noncoding RNAs that posttranscriptionally regulate gene expression and play an important role in multiple cellular processes. A significant percentage of miRNAs are intragenic, which is often functionally related to their host genes playing either antagonistic or synergistic roles. In this study, we constructed and analyzed the entire network of intergenic interactions induced by intragenic miRNAs. We further focused on the core of this network, which was defined as a union of nontrivial strongly connected components, i.e., sets of nodes (genes) mutually connected via directed paths. Both the entire network and its core possessed statistically significant non-random properties. Specifically, genes forming the core had high expression levels and low expression variance. Furthermore, the network core did not split into separate components corresponding to individual signalling or metabolic pathways, but integrated genes involved in key cellular processes, including DNA replication, transcription, protein homeostasis and cell metabolism. We suggest that the network core, consisting of genes mutually regulated by their intragenic miRNAs, could coordinate adjacent pathways or homeostatic control circuits, serving as a horizontal inter-circuit link. Notably, expression patterns of these genes had an efficient prognostic potential for breast and colorectal cancer patients. |
