Search for New Target Genes of MicroRNA for Differential Diagnosis of Benign and Malignant Neoplasms of the Thyroid Gland by In Silico Methods.

Differential diagnosis of thyroid gland neoplasms is an urgent problem in modern oncothyroidology. This is especially true for the diagnosis of follicular thyroid cancer and follicular thyroid adenoma at the preoperative stage. In this study, in silico methods were used to search for potential markers that are microRNA target genes. A list of 19 microRNAs was compiled, the expression of which varies depending on the type of thyroid neoplasms. For these microRNAs, the target genes were selected considering tissue specificity and association with thyroid diseases. We selected 9 target genes (MCM2, RASSF2, SPAG9, SSTR2, TP53BP1, INPP4B, CCDC80, GNAS, and PLK1), which can be considered as promising markers according to published data. Also, 6 new potential markers (CDK4, FGFR1, ERBB3, EGR1, MYLK, and SRC) were found, which make it possible to distinguish between follicular thyroid cancer and follicular thyroid adenoma. The proposed algorithm using various bioinformatics tools allows us to identify potential markers for the differential diagnosis of thyroid neoplasms.

[Microrna, evolution and cancer].

MicroRNAs are known as a posttranscriptional negative regulators of gene expression by binding to the 3'UTP of target mRNAs in cytoplasm. More than 1600 microRNAs expressed in human cells, are involved in the regulation of embryogenesis, differentiation, cell cycle, apoptosis, senescence, thus determining cell fate. Up to 60 % of protein coding genes are under their control. Various sets of microRNAs found in different human tissues under normal and pathological conditions, including cancer, suggest that miRNAs are involved in most cellular pathways. To date, there is no doubt that regulatory potential of the genome is largely determined by miRNAs. In our study, we performed a comparative phylogenetic analysis of the origin and evolution of the total set of 1048 miRNAs in the human genome and investigated the role of certain miRNAs in carcinogenesis of thyroid and mammary glands, as potential diagnostic and prognostic biomarkers of malignancy. Analysis of phylogenetic distribution of miRNAs in the human genome has shown four peaks of appearance of new miRNA genes in the evolution from Methazoa to H. sapiens. The highest amount of new miRNA genes appeared after divergence of H. s. from common ancestor with P. t. Expansion of transposable elements in genome was accompanied by the origin of new miRNA genes on the basis of their sequences. More than 14 % from 1600 miRNAs of human genome originated from mobile elements and still remain. Profiles of expression of 5 miRNAs, pertaining to oncomicroRNAs - miR-21, -221, -222, -155 and -205 - allow distinguishing ductal invasive carcinoma of mammary gland and thyroid papillary carcinoma. The data obtained suggest different ways and roles of participation of the same miRNAs in carcinogenesis of thyroid and mammary glands. So, these miRNAs and profiles of their expression might be used in the diagnosis and prognosis of cancer.