Gilyazova Irina R, Beeraka Narasimha M, Klimentova Elizaveta A, Bulygin Kirill V, Nikolenko Vladimir N, Izmailov Adel A, Gilyazova Gulshat R, Pavlov Valentin N, Khusnutdinova Elsa K, Somasundaram Siva G, Kirkland Cecil E, Aliev Gjumrakch
Institute of Biochemistry and Genetics - Subdivision of the Ufa Federal Research Centre of the Russian Academy of Sciences, Ufa. Russian Federation.
Bashkir State Medical University, Ufa, Russian Federation
Curr Cancer Drug Targets. 2020 Nov 20. doi: 10.2174/1568009620666201120151226.
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.
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.
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).
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.
肾细胞癌占所有成人恶性肿瘤的3%。微小RNA通过与参与细胞凋亡和细胞周期调控的细胞信使核糖核酸相互作用，在各种生物学过程中发挥特定功能。最近的研究报道了VHL - HIF1α信号通路基因的微小RNA结合位点中的单核苷酸多态性（SNP）与肾癌发生和进展之间的潜在关联。
本研究的目的是调查引起VHL - HIF1α信号通路基因与微小RNA结合位点相互作用性质改变的单核苷酸多态性。
本研究纳入了450例经组织学和临床证实的透明细胞肾细胞癌患者以及490例对照。采用TaqMan PCR等位基因鉴别方法进行基因分型。采用Kaplan - Meier统计分析方法分析患者总体生存率。
TSC1基因中的多态性rs10491534与晚期透明细胞肾细胞癌的发生风险显著相关。与55岁及以上的对照组相比，VHL基因中rs1642742的G等位基因在透明细胞肾细胞癌中显著流行（比值比 = 1.5566；可信区间[1.1532 - 2.1019]）。显性模型结合AG或AA基因型个体的结果显示，与GG携带者相比，CDCP1 rs6773576的A等位基因携带者死亡风险更高（风险比3.93，95%可信区间1.76 - 17.21，对数秩检验P = 0.0033）。
本研究阐述了VHL - HIF1α信号通路基因中的微小RNA结合位点变异与透明细胞肾细胞癌风险的关联，这可能影响临床结局。
