[Gene expression profiling in melanoma diagnostics: problems and future application in clinical practice]. / Profilirovanie ekspressii genov v diagnostike melanomy: problemy i perspektivy.

Difficulties in the diagnosis and differential diagnosis of melanoma in the work of a pathologist include not only conflicting structural and morphological features, but also the insufficient effectiveness of biochemical and some molecular markers in immunohistochemical studies. The review presents modern alternative methods for diagnosing malignant tumors based on the assessment of gene expression, the performance, objectivity and reliability of the determination of which may in the future have clinical application as an addition to histopathological methods in the diagnosis and differential diagnosis of various malignant neoplasms, including melanocytic neoplasms, which is changing the paradigm of routine medical practice, introducing diagnostic tests that carry molecular information into it.

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.

[Inhibition of matrix metalloproteinases 9 and 13 affects the degree of lymphocytic infiltration and the expression levels of microRNA miR-21 and miR-let-7b in melanoma cells in vivo].

OBJECTIVE: To estimate changes in the trend of growth of primary tumor nodules, the degree of lymphocytic infiltration, and the expression levels of oncomicroRNA miR-21 and miR-let-7b when inhibiting matrix metalloproteinases 9 and 13 (MMP-9 and MMP-13) in vivo in C57B16 mice with transplantable melanoma B-16. MATERIAL AND METHODS: Tumor growth was evaluated measuring the volume of primary tumor nodules; the degree of lymphocytic infiltration was microscopically estimated using hematoxylin-eosin-stained tissue specimens, by calculating intratumoral lymphocytes. The expression of oncomicroRNA was quantified by real-time PCR. RESULTS: It was shown that MMP-9 and MMP-13 inhibition had no impact on the growth of primary tumor nodules; selective MMP-9 inhibition failed to affect the degree of lymphocytic infiltration of a primary tumor nodule and to change the expression of oncomicroRNA miR-21 and miR-let-7b; the concomitant inhibition of MMP-9 and MMP-13 altered the immunogenic properties of melanoma, stimulated the lymphocytic infiltration of tumor nodules, and decreased the expression of oncomicroRNA miR-21 and miR-let-7b; the degree of lymphocytic infiltration of primary tumor nodules increased in the dynamics of a tumor process and the expression levels of oncomicroRNA remained unchanged. CONCLUSION: The concomitant inhibition of MMP-9 and MMP-13 affects prognosis and survival in skin melanoma.