Projects Laboratory of Genetics Institute of Biology KarRC RAS

Adenosine kinase (ADK) is an important enzyme for maintaining cellular metabolism as it regulates intracellular and extracellular levels of adenosine by phosphorylation to 5'-adenosine monophosphate. ADK has 2 isoforms: nuclear localized, long (ADK-L) and cytoplasmic, short (ADK-S). It is currently assumed that these isoforms may play different roles: if ADK-S is mainly responsible for the routine removal of adenosine, then ADK-L may regulate methylation reactions, including DNA. Extracellular adenosine has an immunosuppressive effect and is a target for cancer treatment. In this regard, the study of adenosine-converting enzymes may be of therapeutic importance.
In the project, at the first stage, the expression of ADK and transcripts of its ADK-L and ADK-S isoforms in the peripheral blood and intestinal tissue of patients with colorectal cancer (CRC) was analyzed. These results indicate a possible involvement of ADK in the pathogenesis of the disease. It was shown that the level of ADK mRNA expression did not change equally in the periphery, where it was lower than the control, and in the tumor, where it was higher than the control.No significant correlation was found between the mRNA level of ADK isoforms and changes in the subpopulation composition of lymphocytes.
At the second stage of the project, the relationship between the level of mRNA of the ADK-L isoform and the degree of methylation of the genes associated with the development of CRC, SEPT9, APC, and FOXP3-TSDR in samples of tumor and normal intestinal tissue from patients with CRC was assessed. The MS-HRM method showed changes in the methylation level of the analyzed genes in tumor tissue samples. However, there was no significant correlation between the ADK-L mRNA level and the degree of methylation of the SEPT9, APC, and FOXP3-TSDR genes in CRC patients.
The second part of the project also analyzed the functioning of CD8+ lymphocytes and Treg cells under experimental conditions close to the tumor microenvironment in the presence of recombinant ADK. These results indicate that rADK can enhance the expression of CD73 ectonucleotidase on CD8+ and CD4+ T cells of CRC patients. And also promote the accumulation of CTLA-4+Treg cells when co-culturing T cells and colorectal cancer cells (Caco-2 and SW837), probably through ADK-S.