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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.

PROONCOGENIC EFFECTS OF INHIBITING THE microRNA miR-106A IN SKIN MELANOMA CELLS IN VITRO.

One of the regulators of gene expression at the post-transcriptional level are miRNAs. Due to its multifunctionality, these molecules are considered as potential targets for controlling the biological behavior of tumor cells. To date, several thousand types of microRNAs have been identified and their expression profiles have shown significant during malignant transformation of cells. In this study, we have investigated the effect of miR-106a functional inhibition on the growth, viability and apoptosis of melanoma cells. Comparative analysis of expression profiles in melanona cells and in cells of melanocytic nevi identified by the use of microarray has revealed a significant increase in the miRNA expression level in melanoma cells. Despite this, inhibition of this molecule in melanoma cells has no antitumor effect on cell proliferation, viability, migration activity and apoptosis of melanoma cells, but increases invasive activity and the ability to form colonies. The paper discusses the importance of evaluating changes in miRNA levels in melanoma and other malignancies, relationship îf miR-106a with the pathogenesis of melanoma, as well as the possible role of miR-106a in other pathologies.

MICRORNAS AS ULTRAVIOLET IRRADIATION EFFECTS REGULATORS IN SKIN CELLS.

MicroRNAs belong to small non-coding RNA which regulate gene expression via mRNA degradation or translation inhibition. MicroRNAs are active modulators of gene expression in the skin caused by exogenous factors including ultraviolet irradiation. These effects are realized by targeting transcription factors and signaling systems components. Changes in microRNAs levels started to register in a few hours after exposure to ultraviolet irradiation, wich confirms the presence of an effective fast processes in the scin cells that modulate the functional status of microRNAs. The reported recently ability of microRNAs to be transported by exosomes may be related to systemic effects of ultraviolet irradiation that include the altered immune response and systemic inflammatory reaction. Understanding these processes is important because of the possibility of purposeful influence on the expression and activity of a microRNA that may have implications for diagnosis and therapy of photodermatosis and malignant skin tumors.

[Molecular and pathomorphological prognostic markers for melanoma: Current approaches and prospects].

The incidence of melanoma demonstrates a persistent increasing tendency, which justifies the need to study and identify new prognostic markers for the development and course of this disease. The given paper shows current approaches to melanoma staging, including those to applying pathomorphological prognostic criteria, and discusses prospects for using the results of genomic and epigenomic studies of the carcinoma in clinical practice.

Russian study of morphological prognostic factors characterization in BRAF-mutant cutaneous melanoma.

Melanoma is one of the aggressive cancer types causing the majority of deaths in skin cancer patients. Mutational screening of the tumor revealed a number of driver mutations in oncogenes which enabled melanoma classification into a few molecular subtypes. BRAF is a key component of mitogen-activated kinase pathway; its activating mutation leads to accelerated melanoma cells proliferation, invasion and survival. Somatic mutations in BRAF were reported in various malignancies, including thyroid cancer, colorectal cancer and melanoma. Specific features of BRAF-positive tumors could have clinical implications as mutational alterations may have an impact on the biological behavior of the tumor and prognosis of the disease. In the present study, the frequency of BRAF V600E mutation was evaluated in Russian patients with melanocytic lesions, of which 41.25% were primary melanoma and 60% were melanocytic nevi. Melanoma patients with trunk localization were of younger age in the BRAF-positive group as compared with BRAF-negative patients. Immunohistochemical evaluations of Ki-67 expression, as well as matrix metalloproteinase-2, -9, were found to be equal in BRAF-positive and BRAF-negative tumors. MMP-2/MMP-9 immunoreactivity was observed in stromal and/or melanocytic cells both in melanoma and nevi patients. Besides tumor cells, MMP-9 expression was observed in lymphocytes in 27.2% of BRAF-positive and in 19.1% of BRAF-negative patients. Histopathological prognostic markers (Breslow thickness, mitotic index, ulceration, tumor infiltrating lymphocytes pattern) did not show any differences depending on BRAF V600E mutational status. The frequency of BRAF-positive melanomas in Russian cohort is similar to other Caucasian population rates. BRAF V600E mutation harboring tumors are more often observed in younger patients without specific features of morphological prognostic factors.

Analysis of the application of MMP-9 inhibitor in skin melanoma: experimental study.

Experiment on C57Bl/6 mice with modeled skin melanoma showed that selective inhibition of matrix metalloproteinase-9 increased lifetime and reduced the number of PCNA(+) tumor cells and intensity of neoangiogenesis. Inhibition of matrix metalloproteinase-9 prevented tumor necrosis. The results suggest that matrix metalloproteinase-9 is involved not only in the regulation of extracellular matrix degradation, but also in the processes of cell proliferation and neoangiogenesis in skin melanoma. Therefore, this enzyme can be considered as a potential therapeutic target.

Changes in the levels of N-cadherin and PCNA in skin melanoma cells are mediated through matrix metalloproteinase 9.

Immunohistochemical studies revealed increased level of matrix metalloproteinase 9 in skin melanoma cells. Inhibition of matrix metalloproteinase 9 with interfering RNA changed the level of PCNA and reduced N-cadherin content in melanoma cells. This attests to the involvement of matrix metalloproteinase 9 in the realization of invasion and metastatic growth and in the regulation of tumor growth and progress.