Changes in the expression of long non-coding RNAs in peripheral blood leucocytes of rheumatoid arthritis patients during methotrexate treatment

Non-coding RNAs play an important role in the regulation of the innate and adaptive immune system both in health and in the development of various pathologies, including autoimmune diseases. Some non-coding RNAs have been identified as promising biomarkers for the rheumatoid arthritis diagnosis. However, many issues related to the mechanism of action, as well as the features of their functioning during interaction with various drugs, still remain unresolved. In this study new data about the long non-coding RNAs BALACAT1, DANCR1, MALAT1 and GAS5 expression in peripheral blood leukocytes of patients with rheumatoid arthritis before therapy and during treatment with the disease-modifying antirheumatic drug methotrexate were obtained. The peripheral blood leukocytes level of BALACAT1, DANCR1 and MALAT1 transcripts were a significantly increase while GAS5 was decrease in patients with rheumatoid arthritis before therapy and in patients resistant to methotrexate compared to the control group of healthy donors and patients with rheumatoid arthritis with a positive response to this treatment (p<0.05). A positive correlation was found between the content of DANCR1, the level of IL6 expression (r=0.55, p=0.01) and the concentration of C-reactive protein (r=0.48, p=0.03). Also a correlation between the studied lncRNAs and the expression of the genes encoding membrane transporters of the ABC (ABCB1) and SLC (RFC1) families was found. The expression level of ABCB1 is in close positive correlation with MALAT1 and BALACAT1 (r=0.49, p<0.001; r=0.64, p<0.05), and the SLC19A1 gene encoding the folate transporter RFC1, with GAS5 (r=0.55; p<0.001). Thus, the results of this study indicate not only the involvement of lncRNA MALAT1, BALACAT1 and GAS5 in the pathogenesis of rheumatoid arthritis, but also their probable participation in the formation of patients' response to the disease-modifying antirheumatic drug methotrexate.