“Биполярное” действие ингибитора васкулогенной мимикрии на экспрессию генов в клетках меланомы

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Abstract

Multiple exogenous or endogenous factors alter gene expression patterns by different mechanisms that yet are poorly understood. We used RNA-Seq analysis in order to study changes in gene expression in melanoma cells capable to vasculogenic mimicry upon action of inhibitor of vasculogenic mimicry. Here, we describe that the drug induces a strong upregulation of 50 genes controlling cell cycle and microtubule cytoskeleton coupled with a strong downregulation of 50 genes controlling different cellular metabolic processes. We found that both groups of genes are simultaneously regulated by multiple sets of transcription factors. We conclude, that one way for coordinated regulation of big groups of genes is the regulation simultaneously by multiple transcription factors.

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About the authors

N. A. Tchurikov

Engelhardt Institute of Molecular Biology Russian Academy of Science

Author for correspondence.
Email: tchurikov@eimb.ru
Russian Federation, Moscow, 119991

A. A. Vartanian

Department of Experimental Diagnosis and Therapy of Tumors, N. N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Email: tchurikov@eimb.ru
Russian Federation, Moscow, 115478

E. S. Klushevskaya

Engelhardt Institute of Molecular Biology Russian Academy of Sciences

Email: tchurikov@eimb.ru
Russian Federation, Moscow, 119991

I. R. Alembekov

Engelhardt Institute of Molecular Biology Russian Academy of Sciences

Email: tchurikov@eimb.ru
Russian Federation, Moscow, 119991

A. N. Kretova

Engelhardt Institute of Molecular Biology Russian Academy of Sciences

Email: tchurikov@eimb.ru
Russian Federation, Moscow, 119991

V. R. Сhechetkin

Engelhardt Institute of Molecular Biology Russian Academy of Sciences

Email: tchurikov@eimb.ru
Russian Federation, Moscow, 119991

G. I. Kravatskaya

Engelhardt Institute of Molecular Biology Russian Academy of Sciences

Email: tchurikov@eimb.ru
Russian Federation, Moscow, 119991

V. S. Kosorukov

Department of Experimental Diagnosis and Therapy of Tumors, N. N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Email: tchurikov@eimb.ru
Russian Federation, Moscow, 115478

Yu. V. Kravatsky

Engelhardt Institute of Molecular Biology Russian Academy of Sciences

Email: tchurikov@eimb.ru
Russian Federation, Moscow, 119991

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Supplementary files

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2. Fig. 1. Heat map of gene expression changes in melanoma cells under the influence of a vasculogenic mimicry inhibitor. Fifty genes were selected for each gene whose expression changed maximally (increased or decreased) under the influence of the inhibitor. A color scale of expression changes in log2FC is shown. The 50 genes whose expression increased correspond to the logFC > 1.71 criterion (i.e., their expression increased by more than 3.27 times). The 50 genes whose expression decreased correspond to the log2FC < 1.89 criterion (i.e., their expression decreased by more than 3.7 times).

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3. Fig. 2. Genes whose expression changed under the influence of the inhibitor (Input Genes) are regulated simultaneously by many FTs (Enriched Terms). a – Genes whose expression increased. b – Genes whose expression decreased. The results were obtained using the Enrichr database (https://maayanlab.cloud/Enrichr/enrich) to search for FTs that simultaneously regulate genes (Enrichr Submissions TF-Gene Coocurrence).

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4. Fig. 3. Schematic showing how adding an inhibitor disrupts the gene expression balance and how this affects the phenotype of melanoma cells. a – Gene expression balance before adding the inhibitor. Spindle-shaped cells on Matrigel form vessel-like structures. b – Disruption of the gene expression balance causes changes in cell behavior (formation of vessel-like structures is disrupted) and their shape (cells are more rounded).

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