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Investigation of the Role of microRNA Associated with the VHL-HIFα-Dependent Pathway in Patients with Clear Cell Renal Cell Carcinoma

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Abstract

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.

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Funding

This work was performed on the equipment of the Biomika Shared Access Center and the unique KODINK scientific facility, using DNA samples from the Shared Access Center Collection of Human Biological Materials of the Institute of Biochemistry and Genetics, Ufa Federal Research Centre, Russian Academy of Sciences, and with financial support from the Russian Science Foundation (project no. 20-15-00209).

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    Authors and Affiliations

    1. Institute of Biochemistry and Genetics, Ufa Federal Research Centre, Russian Academy of Sciences, 450054, Ufa, Russia

      E. A. Klimentova, I. R. Gilyazova, M. A. Bermisheva & E. K. Khusnutdinova

    2. Bashkir State Medical University, 450008, Ufa, Russia

      A. M. Blinnikova, R. I. Safiullin, A. A. Izmailov, V. N. Pavlov & E. K. Khusnutdinova

    3. Harbin Medical University, 150081, Harbin, Heilongjiang, P.R. China

      B. Yang

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    1. E. A. Klimentova
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    2. I. R. Gilyazova
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    E.A. Klimentova and I.R. Gilyazova equally contributed to this study.

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    Statement of compliance with standards of research involving humans as subjects. All procedures performed in a study involving people comply with the ethical standards of the institutional and/or national committee for research ethics and the 1964 Helsinki Declaration and its subsequent changes or comparable ethical standards. Informed consent was obtained from each of the participants in the study.

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    Klimentova, E.A., Gilyazova, I.R., Bermisheva, M.A. et al. Investigation of the Role of microRNA Associated with the VHL-HIFα-Dependent Pathway in Patients with Clear Cell Renal Cell Carcinoma. Russ J Genet 56, 363–369 (2020). https://doi.org/10.1134/S1022795420030096

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