Реферат: Uveal melanoma (UM) develops from melanocytes of the uveal tract and makes up about 5% of all melanoma cases The spread of UM cells is hematogenous and the largest number of UM metastases is detected in the liver. There is a poor understanding of the role of epithelial–mesenchymal transition (EMT) in UM progression. By analogy with other tumours, it can be assumed that targeting of regulators of this process may reduce the growth of the tumour node and metastasis spread. Since hypoxia is a major stimulator of EMT, we investigated the interaction of proteins under the control of the hypoxia-inducible factor 1α (HIF-1α): ZEB1, VEGFA and melanoma antigen family gene D2 (MAGE-D2). Ten UM cell lines were used as models. ZEB1-hyperexpression cell line was derived from ZEB1-deficient cell line using lentiviral transduction. We found that hyperexpression of ZEB1 mRNA in transgenic cells stimulated a 30-fold increase in mRNA VEGF receptor level relative to parental cells. We constructed correlation curves between ZEB1, MAGE-D2 expression and VEGFA secretion under normoxia and hypoxia. Interestingly, all cultures examined had the phenotype of E-cadlow/N-cadlow, and ZEB1 mRNA levels differed significantly. All UM cells expressed MAGE-D2 mRNA under normoxia conditions, and MAGE-D2 mRNA was also increased under hypoxia. Human UM cells are more typical by the expression of MAGE-D2 mRNA than ZEB1. MAGE-D2 may be a target for anti-UM therapy. ZEB1 may be involved in the development of UM cell resistance to anti-VEGF drugs.

Библиографическая ссылка: Koval O.A. , Zhilnikova M.V. , Zvereva S.P. , Biryukov M.M. , Balantaeva M.N. , Chernih D.V. , Stanishevskaya O.M. , Atamanov V.V.
Interaction of ZEB1 with VEGFA, and MAGE-D2 in uveal melanoma
FEBS OPEN BIO. 2025. V.15. N2. P.259. DOI: 10.1002/2211-5463.70071 OpenAlex

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Опубликована в печати:

29 июл. 2025 г.

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OpenAlex:

W4412764642

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