Vol 55(2021) N 4 p. 610-617; DOI 10.1134/S0026893321020199
I.Yu. Dubovtseva1, M.B. Aksenenko1, E.D. Nikolaeva1, A.S. Averchuk1, A.V. Moshev3, A.A. Savchenko3, S.V. Markova2, T.G. Ruksha1*
-Mediated Effects of miR-204-5p on Melanoma Cell Proliferation1Voino-Yasenetsky Krasnoyarsk State Medical University, Ministry of Health of the Russian Federation, Krasnoyarsk, 660022 Russia
2Biophysics Institute of the Siberian Branch of the RAS - Division of Federal Research Center "Krasnoyarsk Scientific Center of the Siberian Branch of the RAS", Krasnoyarsk, 660022 Russia
3Research Institute for Medical Problems in the North, Siberian Branch of the Russian Academy of Sciences, Krasnoyarsk, 660022 Russia
Received - 2020-08-17; Revised - 2020-10-24; Accepted - 2020-11-11
MicroRNAs epigenetically regulate physiological and pathological processes. Previously, we found that miR-204-5p is expressed at low levels in melanoma cells, and an increase in its level leads to a change in proliferation, migration, and invasion of these cancer cells. Now, using bioinformatics analysis, it has been shown that the target of miR-204-5p is FOXC1 transcription factor, which is implicated in carcinogenesis. Using the luciferase reporter assay, it was found that miR-204-5p suppresses expression of the FOXC1 gene by binding to its 3' non-coding region. Transfection of small interfering RNA (siRNA) targeting FOXC1 into melanoma cells caused a decrease in miR-204-5p levels, which is consistent with the generally accepted concept of feedback regulation of miRNA expression by target genes. According to the results of the MTT test and fluorescence microscopy, the proliferation level of melanoma cells under the influence of siRNA to FOXC1 decreased 72 h after transfection. Changes in the ratio of cells by cell cycle phase were analyzed using flow cytometry. Regulatory relationships between FOXC1 and miR-204-5p, and an inhibitory effect of FOXC1 knockdown on melanoma cell proliferation were revealed. Based on the results, it can be assumed that miR-204-5p regulates proliferation of melanoma cells by affecting FOXC1 expression.
FOXC1, miR-204-5p, melanoma, BRO, SK-MEL-2, siRNA, miRNA, dormant cancer cells