Почечно-клеточная карцинома (ПКК) является распространенной почечной неоплазией различных морфологических типов, среди которых светлоклеточная ПКК встречается наиболее часто. Считается, что семейство микроРНК-29, включающее микроРНК-29a, микроРНК-29b и микроРНК-29c, связано с агрессивностью и прогнозом течения злокачественных новообразований и может быть перспективным биомаркером для прогнозирования инициации, прогрессирования и патогенеза рака. Уровни экспрессии микроРНК-29a, -29b и -29c были определены в 30 парах образцов нормальной и опухолевой ткани почки пациентов с скПКК с использованием количественной ПЦР в реальном времени. Было обнаружено статистически значимое снижение экспрессии микроРНК-29a (Fold change=0,213; р-value=0,0016) в опухолевой ткани по сравнению с нормальной почечной паренхимой. Renal cell carcinoma (RCC) is a common renal neoplasia of various morphological types, among which clear cell RCC is most common. It is believed that the miRNA-29 family, including miRNA-29a, miRNA-29b and miRNA-29c, is associated with aggressiveness and prognosis of malignant neoplasms and can be a promising biomarker for predicting the initiation, progression and pathogenesis of cancer. Expression levels of miRNA-29a, -29b, and -29c were determined in 30 pairs of normal and tumor tissue samples from the kidneys of patients with RCC using real-time quantitative PCR. A statistically significant decrease in miRNA-29a expression was found (Fold change = 0.213; p-value = 0.0016) in tumor tissue compared with normal renal parenchyma.

Renal cell carcinoma (RCC) is a common renal neoplasia of various morphological types, among which clear cell RCC is the most common. About 70% of sporadic cases of clear cell renal cell carcinoma are accompanied by inactivation of the von Hippel–Lindau gene ( VHL ). It is known that VHL is a target for several miRNAs—small noncoding RNAs that carry out post-transcriptional regulation of genes. The purpose of this study was to analyze the expression levels of miRNAs which target the VHL gene and also to analyze the association of genotypes and alleles of the rs1642742 polymorphic locus of the VHL gene located at the miRNA binding site with the risk of developing clear cell renal cell carcinoma (ccRCC). As a result of the analysis, no statistically significant changes in the expression level were found, although miR-21 and miR-224 showed a tendency to increase expression in the tumor compared with normal kidney tissue ( p = 0.0597 and p = 0.0846, respectively). Also, in a comparative analysis of the frequencies of genotypes and alleles of the polymorphic locus rs1642742 of the VHL gene, an association of the rs1642742*GG genotype was found with the risk of developing ccRCC in a group of people over 55 years old ( p = 0.0381; OR = 1.84; 95% CI (1.03–3.31)). Undoubtedly, further study of miRNAs on large groups of samples is necessary, which will make it possible both to identify new molecular markers of the risk of developing the disease and to form panels of prognostic markers.

Introduction. Much attention in ccRCC development is paid to VHL-HIF1α pathway genes. Numerous genes involved in the pathogenesis of ccRCC are targets for miRNA. Alteration in the nature of interaction with miRNA binding site as a result of a single nucleotide substitution may promote change the expression of target genes involved in the genesis and development of tumors.Purpose of research. Analysis of the role of polymorphic variants in the miRNA binding sites of the VHL-HIF1α gene pathways in ccRCC development.Materials and methods. We used 225 DNA samples isolated from the venous blood of ccRCC patients who are hospitalized to the Clinic of the Bashkir State Medical University, and 298 healthy individuals. The genotyping of miRNA binding site polymorphisms in VHL-HIFα-dependent pathway genes (rs10982724 of the DEC1 gene, rs406271 of the TFRC gene, rs10491534 of the TSC1 gene, rs1642742 of the VHL gene, rs3025033 of the VEGFA gene) was performed using Taq-man assays.Results. The frequency distribution of alleles and genotypes of rs1642742 of the VHL gene showed that rs1642742 *GG is a marker of the increased risk for ccRCC. In addition, rs10491534 * C allele was found to be the marker for severe ccRCC (p = 0.044; OR = 1.72 (CI = 1.012-2.911)), and rs10491534 * TT genotype (p = 0.044; OR = 0.55; (95% CI = 0.31–0.98)) of the TSC1 gene was shown to be a protective marker for ccRCC of severe duration.Conclusions. The study indicated the association of miRNA binding sites polymorphisms with the risk of ccRCC development and severity of disease. However, further studies of the genes are needed to establish their functional significance and role in the pathogenesis of ccRCC.

Introduction. Much attention in ccRCC development is paid to VHL-HIF1α pathway genes. Numerous genes involved in the pathogenesis of ccRCC are targets for miRNA. Alteration in the nature of interaction with miRNA binding site as a result of a single nucleotide substitution may promote change the expression of target genes involved in the genesis and development of tumors. Purpose of research. Analysis of the role of polymorphic variants in the miRNA binding sites of the VHL-HIF1α gene pathways in ccRCC development. Materials and methods. We used 225 DNA samples isolated from the venous blood of ccRCC patients who are hospitalized to the Clinic of the Bashkir State Medical University, and 298 healthy individuals. The genotyping of miRNA binding site polymorphisms in VHL-HIFα-dependent pathway genes (rs10982724 of the DEC1 gene, rs406271 of the TFRC gene, rs10491534 of the TSC1 gene, rs1642742 of the VHL gene, rs3025033 of the VEGFA gene) was performed using Taq-man assays. Results. The frequency distribution of alleles and genotypes of rs1642742 of the VHL gene showed that rs1642742 *GG is a marker of the increased risk for ccRCC. In addition, rs10491534 * C allele was found to be the marker for severe ccRCC (p = 0.044; OR = 1.72 (CI = 1.012-2.911)), and rs10491534 * TT genotype (p = 0.044; OR = 0.55; (95% CI = 0.31–0.98)) of the TSC1 gene was shown to be a protective marker for ccRCC of severe duration. Conclusions. The study indicated the association of miRNA binding sites polymorphisms with the risk of ccRCC development and severity of disease. However, further studies of the genes are needed to establish their functional significance and role in the pathogenesis of ccRCC.

Kidney cancer is a heterogeneous group of malignant tumors, the vast majority of which are renal cell carcinomas (RCC) of various morphological types, of which the most common is the clear cell renal cell carcinoma (ccRCC). Particular attention in the carcinogenesis of the ccRCC is given to a number of tumor suppressor genes located on the short arm of the third chromosome. One of these genes, which are inactivated in the case of ccRCC is the PBRM1 gene encoding the PBAF SWI/SNF subunit of the chromatin remodeling complex, BAF180. The PBRM1 gene is located on the short arm of the third chromosome in the 3p21 region near the von Hippel-Lindau gene (VHL), the mutation in which is the main event in the occurrence of ccRCC. The aim of our investigation is identification of changes in the nucleotide sequence of the PBRM1 tumor suppressor gene in patients with ccRCC. 210 pairs of DNA samples isolated from ccRCC tissue were studied. Analysis of changes in the nucleotide sequence of DNA was carried out by HRM analysis and direct sequencing. In the PBRM1 gene, two somatic mutations were found (c.233G>A (p.D45N) in exon 2, c.1675-1676delTC in exon 15) which were not described previously, and one known polymorphic variant rs17264436 (in exon 23). The frequency of detected mutations was 0.95 % of cases. Analysis of the allelic association for the polymorphic locus rs17264436 showed a statistically significant increase in the risk of developing advanced kidney cancer in carriers of allele rs17264436*A, which can be used in the development of prognostic marker panels. Perhaps the low frequency of mutations in the samples we studied is due to the fact that the inactivation of the PBRM1 gene takes place in other ways, and may also be due to the ethno-specificity of the studied group of patients.

Small non-coding RNAs (microRNAs) are involved in almost all biological mechanisms of carcinogenesis. Due to their stability in biological fluids microRNAs may serve a perspective biomarker for diagnosis and prognosis of oncological diseases. The review is dedicated to the analysis of microRNAs, as potential diagnostic markers of urological malignancies. Recent advances in the knowledge of miRNAs origin in body fluids, their stability and application as a potentially new class of biomarkers in medicine are summarized and discussed in the article.

The results of the whole-exome DNA sequencing of eight prostate adenocarcinoma patients are presented. DNA was isolated from the peripheral blood as well as healthy and tumor prostate tissue from each patient. Bioinformatics analysis was conducted and the most significant mutations in prostate cancer patients were revealed. The obtained data could be important for understanding of the molecular mechanisms of prostate cancer pathogenesis and facilitate development of new approaches for treatment of the disease.