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Novel MicroRNA Binding Site SNPs and the Risk of Clear Cell Renal Cell Carcinoma (ccRCC): A Case-Control Study

[ Vol. 21 , Issue. 3 ]

Author(s):

Irina R. Gilyazova, Narasimha M. Beeraka, Elizaveta A. Klimentova, Kirill V. Bulygin, Vladimir N. Nikolenko, Adel A. Izmailov, Gulshat R. Gilyazova, Valentin N. Pavlov, Elsa K. Khusnutdinova, Siva G. Somasundaram, Cecil E. Kirkland and Gjumrakch Aliev*Pages 203-212 (10)

Abstract:


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 the SNPs invoking an alteration in the nature of interaction with miRNA binding sites of VHL-HIF1α pathway genes.

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 the risk of developing advanced ccRCC. Allele G of rs1642742 in VHL gene was significantly prevalent in ccRCC compared with the 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 a 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 the clinical outcomes.

Keywords:

Renal cell carcinoma, miRNA, VHL-HIF1α pathway, polymorphism, epigenetics.

Affiliation:

Institute of Biochemistry and Genetics - Subdivision of the Ufa Federal Research Centre of the Russian Academy of Sciences, Ufa, Center of Excellence in Regenerative Medicine and Molecular Biology (CEMR), Department of Biochemistry, JSS Academy of Higher Education and Research (JSS AHER), Mysuru, Karnataka, Institute of Biochemistry and Genetics - Subdivision of the Ufa Federal Research Centre of the Russian Academy of Sciences, Ufa, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), 8/2 Trubetskaya Str., Moscow, 119991, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), 8/2 Trubetskaya Str., Moscow, 119991, Bashkir State Medical University, Ufa, Bashkir State Medical University, Ufa, Bashkir State Medical University, Ufa, Bashkir State Medical University, Ufa, Department of Biological Sciences, Salem University, Salem, WV, 26426, Department of Biological Sciences, Salem University, Salem, WV, 26426, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), 8/2 Trubetskaya Str., Moscow, 119991

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