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Current Cancer Drug Targets

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*

DOI: 10.2174/1568009620666201120151226

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

Page: [203 - 212] Pages: 10

  • * (Excluding Mailing and Handling)

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.

Graphical Abstract

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