| Autor: |
Tchurikov NA; Department of Epigenetic Mechanisms of Gene Expression Regulation, Engelhardt Institute of Molecular Biology Russian Academy of Sciences, 119334 Moscow, Russia., Vartanian AA; Department of Experimental Diagnosis and Therapy of Tumors, N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia, 115478 Moscow, Russia., Klushevskaya ES; Department of Epigenetic Mechanisms of Gene Expression Regulation, Engelhardt Institute of Molecular Biology Russian Academy of Sciences, 119334 Moscow, Russia., Alembekov IR; Department of Epigenetic Mechanisms of Gene Expression Regulation, Engelhardt Institute of Molecular Biology Russian Academy of Sciences, 119334 Moscow, Russia., Kretova AN; Department of Epigenetic Mechanisms of Gene Expression Regulation, Engelhardt Institute of Molecular Biology Russian Academy of Sciences, 119334 Moscow, Russia., Lukicheva VN; Department of Epigenetic Mechanisms of Gene Expression Regulation, Engelhardt Institute of Molecular Biology Russian Academy of Sciences, 119334 Moscow, Russia., Chechetkin VR; Department of Epigenetic Mechanisms of Gene Expression Regulation, Engelhardt Institute of Molecular Biology Russian Academy of Sciences, 119334 Moscow, Russia., Kravatskaya GI; Department of Epigenetic Mechanisms of Gene Expression Regulation, Engelhardt Institute of Molecular Biology Russian Academy of Sciences, 119334 Moscow, Russia., Kosorukov VS; Department of Experimental Diagnosis and Therapy of Tumors, N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia, 115478 Moscow, Russia., Kravatsky YV; Department of Epigenetic Mechanisms of Gene Expression Regulation, Engelhardt Institute of Molecular Biology Russian Academy of Sciences, 119334 Moscow, Russia.; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology Russian Academy of Sciences, 119334 Moscow, Russia. |
| Abstrakt: |
Gene expression patterns are very sensitive to external influences and are reflected in phenotypic changes. It was previously described that transferring melanoma cells from a plastic surface to Matrigel led to formation of de novo vascular networks-vasculogenic mimicry-that are characteristic to a stemness phenotype in aggressive tumors. Up to now there was no detailed data about the gene signature accompanying this process. Here, we show that this transfer shortly led to extremely strong epigenetic changes in gene expression in the melanoma cells. We observed that on Matrigel numerous genes controlling ribosome biogenesis were upregulated. However, most of the activated genes were inhibitors of the differentiation genes ( ID1 , ID2 , and ID3 ). At the same time, the genes that control differentiation were downregulated. Both the upregulated and the downregulated genes are simultaneously targeted by different transcription factors shaping sets of co-expressed genes. The specific group of downregulated genes shaping contacts with rDNA genes are also associated with the H3K27me3 mark and with numerous lincRNAs and miRNAs. We conclude that the stemness phenotype of melanoma cells is due to the downregulation of developmental genes and formation of dedifferentiated cells. |
