Registration Number
0217U000653,
0112U002197
, R & D reports
Title
Molecular epidemiology of metal-containing proteins at tumo-host interaction.
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Head
Chekhun Vasyl Fedorovych,
Registration Date
17-02-2017
Organization
R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology
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We have established that the formation of drug resistance both to cisplatin and doxorubicin is accompanied by changes in the ratio of metal-containing proteins at the tumor and the organism levels. As the example, in animals with resistant strains Guerin carcinoma we found significantly reduced the activity of serum ceruloplasmin and observed violations of expression of circulating miR-122, which is involved in the iron metabolism. In tumor tissue of both resistant strains, we determined a high degree of promoter methylation of transferrin receptor 1 gene and increase of ferritin level compared with the original strain of Guerin carcinoma, indicating a depletion of iron in tumor cells. A distinguishing feature of doxorubicin-resistant Guerin carcinoma is a significant reduction in miR-320a level, which regulates the expression of MDR1, that contributes to the activation of cytotoxic agents output and protection from oxidative stress. Tumor cells from resistant to cisplatin strain were characterized by increased expression of miR-133a, downregulation of miR- 122 and -34a which may indicate reducing the effectiveness of p53-mediated apoptosis induced by DNA damage. The most significant changes in rates of exchange and epigenetic regulation of metal-containing proteins in the tumor and in the body we have found on the terminal growth phase of sensitive and resistant strains of Guerin's carcinoma, indicating depletion of iron not only in body but also in the tumor because it is essential for active tumor growth and proliferation. Also, we have demonstrated that 5-azacitidin usage as a remedy has marked effect on the metabolism of metal metabolism proteins (ferritin, transferrin, ceruloplasmin) in serum and tumor tissue of animals with Guerin carcinoma. We have proved that the effect of 5-azacitidine was implemented at the epigenetic level and caused changes in the degree of methylation of heavy chain ferritin and transferrin receptor 1 genes and microRNA expression (miR-200b, -133a, -320a), associated with the expression of investigated proteins.
Product Description
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Бережна Н.М.
Божко І.В.
Борікун Т.В.
Вертелецька О.І.
Демаш Д.В.
Задворний Т.В.
Коноваленко В.Ф.
Кунська Л.М.
Лозовська Ю.В.
Лук'янова Н.Ю.
Мельник Н.М.
Налєскіна Л.А.
Півнюк В.М.
Павлова А.О.
Поліщук Л.З.
Пономарьова О.В.
Сторчай Д.М.
Терновий М.К.
Тодор І.М.
Трембач Л.В.
Чепурнатий М.В.
Чехун В.Ф.
Яловенко Т.М.
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2020-04-02
