CIRCULATION MICRORNA AS A POSSIBLE PREDICTOR OF ANTHRACYCLINE-INDUCED CARDIOTOXICITY

Introduction. Doxorubicin is an anthracycline antibiotic widely used in the treatment of malignant neoplasms. Anthracyclines have been shown to have an undesirable side effect associated with the development of cardiotoxic effects. Today, a promising direction in fundamental and practical medicine is the search for highly sensitive, highly specific markers for the early diagnosis of cardiotoxic effects of anthracycline antibiotics. Thus, for the last five years, special attention has been paid to circulating miRNAs, which are small sequences (19-25 nucleotides) and regulate gene expression at the post-transcriptional level. An important role of microRNAs in many physiological and pathological processes is noted, and therefore they can be considered as diagnostic and therapeutic targets.

Purpose of the study: To assess the level of expression of circulating miRNAs in dynamics in patients with breast cancer receiving anthracyclines therapy.

Materials and methods. In 15 women with a verified diagnosis of breast cancer, whose therapy included anthracyclines, venous blood was taken into vacutainers with K3EDTA at two time points: before the start of treatment and 6 months after the start of chemotherapy. The resulting plasma, after centrifugation, was used for microRNA isolation using commercial kits from Qiagen (cat. no. 217184). The amount of isolated miRNA was measured on a Qubit 4 instrument (Thermofisher Scientific, USA) using the Qubit™ microRNA Assay Kits (cat. no. Q32881). The level of circulating miRNAs (hsa-mir-1-3p, hsa-mir-200a-3p, hsa-mir-21-3p, hsa-mir-133b, hsa-mir-429, hsa-mir -30a-3p). hsa-mir-486-5p was used to normalize the results. The relative expression level was calculated using the ΔСt method. The results were expressed as fold change. Statistical processing was carried out using the program "GraphPad Prism 8".

Results. The study showed a change in the expression level of circulating miRNAs 6 months after the start of anthracycline therapy. A significant decrease in the expression of the following circulating miRNAs was revealed: hsa-mir-1-3p, hsa-mir-200a-3p, hsa-mir-133b, hsa-mir-30a-3p. For hsa-mir-21-3p and hsa-mir-429 no statistically significant differences were obtained.

Conclusions. Four microRNAs were identified, the expression of which decreases 6 months after doxorubicin administration, which indicates the influence of anthracyclines on gene expression and, possibly, on the epigenetic regulation of pathological processes associated with cardiotoxic effects of therapy. Validation of the expression in a larger sample of patients is required to confirm the results obtained.