The Effect of Cell-Free DNA from Blood Serum of Mice with Metastatic Melanoma on Enhancement of Oncogenic Properties of Melanoma Cells

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Alina A. Filatova^1,2,a, Ludmila A. Alekseeva^1,b, Innokenty A. Savin^1,c, Aleksandra V. Sen’kova^1,d, Marina A. Zenkova^1,e, and Nadezhda L. Mironova^1,f*

¹Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia

²Novosibirsk State University, 630090 Novosibirsk, Russia

^* To whom correspondence should be addressed.

Received January 31, 2023; Revised March 13, 2023; Accepted March 13, 2023

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Currently, a significant increase in the levels of circulating cell-free DNA (cfDNA) in the blood of patients is considered as a generally recognized marker of the development of oncological diseases. Although the tumor-associated cfDNA has been well studied, its biological functions remain unclear. In this work, we investigated the effect of cfDNA isolated from the blood serum of the mice with B16-F10 metastatic melanoma on the properties of the B16-F10 melanoma cells in vitro. It was found that the profile of cfDNA isolated from the blood serum of mice with melanoma differs significantly from the cfDNA isolated from the blood serum of healthy mice, and is similar to the genomic DNA of B16 cells with regards to abundance of oncogenes and mobile genetic elements (MGE). It was shown that the cfDNA of mice with melanoma penetrated into B16 cells, resulting in the increase in abundance of oncogenes and MGE fragments, and caused 5-fold increase of the mRNA level of the secreted DNase Dnase1l3 and a slight increase of the mRNA level of the Jun, Fos, Ras, and Myc oncogenes. cfDNA of the healthy mice caused increase of the mRNA level of intracellular regulatory DNase EndoG and 4-fold increase of the mRNA level of Fos and Ras oncogenes, which are well-known triggers of a large number of signal cascades, from apoptosis inhibition to increased tumor cell proliferation. Thus, it is obvious that the circulating cfDNA of tumor origin is able to penetrate into the cells and, despite the fact that no changes were found in the level of viability and migration activity of the tumor cells, cfDNA, even with a single exposure, can cause changes at the cellular level that increase oncogenicity of the recipient cells.

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KEY WORDS: circulating cell-free DNA, melanoma B16

DOI: 10.1134/S0006297923070118

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