Email this article Methylation of the genes for the microRNAs miR-129-2 and miR-9-1, changes in their expression, and activation of their potential target genes in clear cell renal cell carcinoma
- Authors: Pronina I.V.1,2, Klimov E.A.3, Burdennyy A.M.2,4, Beresneva E.V.5, Fridman M.V.6, Ermilova V.D.7, Kazubskaya T.P.7, Karpukhin A.V.1, Braga E.A.1,2, Loginov V.I.1,2
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Affiliations:
- Research Centre of Medical Genetics
- Institute of General Pathology and Pathophysiology
- Biological Faculty, Moscow State University
- Emanuel Institute of Biochemical Physics
- State Research Institute of Genetics and Selection of Industrial Microorganisms
- Vavilov Institute of General Genetics
- Cancer Research Center
- Issue: Vol 51, No 1 (2017)
- Pages: 61-71
- Section: Molecular Cell Biology
- URL: https://journal-vniispk.ru/0026-8933/article/view/162931
- DOI: https://doi.org/10.1134/S0026893316060169
- ID: 162931
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Abstract
Methylation of promoter CpG islands and microRNA (miRNA) interactions with mRNAs of target genes are epigenetic mechanisms that play a crucial role in deregulation of gene expression and signaling pathways in tumors. Altered expression of six chromosome 3p genes (RARB(2), SEMA3B, RHOA, GPX1, NKIRAS1, and CHL1) and two miRNA genes (MIR-129-2 and MIR-9-1) was observed in primary clear cell renal cell carcinomas (ccRCCs, 31–48 samples) by RT-PCR and qPCR. Significant downregulation (p < 0.05, Fisher’s exact test) was observed for SEMA3B, NKIRAS1, and CHL1; and differential expression, for the other chromosome 3p and miRNA genes. Methylation-specific PCR with primers to RARB(2), SEMA3B, MIR-129-2, and MIR-9-1 showed that their methylation frequency was significantly (p < 0.05, Fisher’s exact test) elevated in the ccRCC samples. Significant correlations between promoter methylation and expression were confirmed for SEMA3B and observed for the first time for RARB(2), GPX1, and MIR-129-2 in ccRCC (Spearman’s correlation coefficient rs ranging 0.31–0.60, p < 0.05). The MIR-129-2 and RARB(2) methylation frequencies significantly correlated with ccRCC progression. MIR-129-2 methylation correlated with upregulation of RARB(2), RHOA, NKIRAS1, and CHL1 (rs ranging 0.35–0.53, p < 0.05). The findings implicate methylation in regulating RARB(2), SEMA3B, GPX1, and MIR-129-2 and indicate that miR-129-2 and methylation of its gene affect RARB(2), RHOA, NKIRAS1, and CHL1 expression.
About the authors
I. V. Pronina
Research Centre of Medical Genetics; Institute of General Pathology and Pathophysiology
Author for correspondence.
Email: zolly_sten@mail.ru
Russian Federation, Moscow, 115478; Moscow, 125315
E. A. Klimov
Biological Faculty, Moscow State University
Email: zolly_sten@mail.ru
Russian Federation, Moscow, 119234
A. M. Burdennyy
Institute of General Pathology and Pathophysiology; Emanuel Institute of Biochemical Physics
Email: zolly_sten@mail.ru
Russian Federation, Moscow, 125315; Moscow, 119334
E. V. Beresneva
State Research Institute of Genetics and Selection of Industrial Microorganisms
Email: zolly_sten@mail.ru
Russian Federation, Moscow, 117545
M. V. Fridman
Vavilov Institute of General Genetics
Email: zolly_sten@mail.ru
Russian Federation, Moscow, 117971
V. D. Ermilova
Cancer Research Center
Email: zolly_sten@mail.ru
Russian Federation, Moscow, 115478
T. P. Kazubskaya
Cancer Research Center
Email: zolly_sten@mail.ru
Russian Federation, Moscow, 115478
A. V. Karpukhin
Research Centre of Medical Genetics
Email: zolly_sten@mail.ru
Russian Federation, Moscow, 115478
E. A. Braga
Research Centre of Medical Genetics; Institute of General Pathology and Pathophysiology
Email: zolly_sten@mail.ru
Russian Federation, Moscow, 115478; Moscow, 125315
V. I. Loginov
Research Centre of Medical Genetics; Institute of General Pathology and Pathophysiology
Email: zolly_sten@mail.ru
Russian Federation, Moscow, 115478; Moscow, 125315
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