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Background: Renal cell carcinoma represents 3% of all adult malignancies. MicroRNAs exhibit specific functions in various biological processes through their interaction with cellular mRNA involved in apoptosis and cell cycle control. Recent studies have reported the potential association of single-nucleotide polymorphisms (SNPs) in miRNA-binding sites of VHL-HIF1α pathway genes with renal cancer development and progression. Objective: The objective of this study is to investigate SNPs invoking an alteration in the nature of interaction with miRNA binding sites of VHL-HIF1α pathway genes. Patients & Methods: Total 450 cases of histologically and clinically verified ccRCC and 490 controls were included in our study. Genotyping was performed using a TaqMan PCR allelic discrimination method. Kaplan-Meier method of statistical analysis was implemented to analyze the overall patient survival rate. Results : Polymorphism rs10491534 in TSC1 gene was significantly associated with risk of developing advanced ccRCC. Allele G of rs1642742 in VHL gene was significantly prevalent in ccRCC compared with control group aged 55 and older (OR = 1.5566; CI [1.1532-2.1019]). Results from the dominant model combining individuals with AG or AA genotype showed that the A allele bearers of CDCP1 rs6773576 exhibited higher risk of death compared to GG carriers (HR 3.93, 95% CI 1.76-17.21, log-rank P = 0.0033). Conclusion: The present study delineated the association of miRNA binding site variants in VHL-HIF1α pathway genes with the ccRCC risk, which may affect clinical outcome.

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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.