Role of sirtuin 1 in regulation of melanoma cell proliferation

Melanoma remains one of the most dangerous skin cancers among fair-skinned population. The search for new effective treatments, including therapy based on the selection of molecular targets, is one of the main and difficult tasks in the study of melanoma. One of the trends in experimental oncology is the study of microRNA's role in carcinogenesis. MicroRNAs are involved in many physiological and pathological processes, including cell proliferation, differentiation, migration, invasion, and carcinogenesis. It has been previously revealed that miR-204-5p levels are reduced in malignant tumors, in particular, in skin melanoma. The aim of this study was to determine the functional role of SIRT1 as a direct target of miR-204-5p in the pathogenesis of skin melanoma. Bioinformatics analysis allowed identification of micrRNA target genes that affected apoptosis, proliferation and cell viability. The level of proliferation of melanoma cells under the influence of small interfering RNA was estimated using the MTT test and fluorescence microscopy. Luciferase Reporter assay was performed to evaluate whether SIRT1 was a target of miR-204-5p. Relative luciferase activity was calculated 48 hours after transfection with miR-204-5p mimic. The MTT test showed that the proliferative activity of melanoma cells decreased 72 hours after siRNA SIRT1 knockdown. Fluorescent microscope revealed the same tendency in SIRT1 siRNA transfected cells. Mechanistic studies revealed that miR-204-5p repressed the expression of SIRT1 through binding to its 3'UTR. Therefore, miR-204-5p can regulate melanoma cell proliferation by targeting SIRT1 which can affect intercellular signaling systems related to cell cycle.