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

I. V. Pronina; E. A. Klimov; A. M. Burdennyy; E. V. Beresneva; M. V. Fridman; V. D. Ermilova; T. P. Kazubskaya; A. V. Karpukhin; E. A. Braga; V. I. Loginov

doi:10.1134/S0026893316060169

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

Autores: 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
Afiliações:
1. Research Centre of Medical Genetics
2. Institute of General Pathology and Pathophysiology
3. Biological Faculty, Moscow State University
4. Emanuel Institute of Biochemical Physics
5. State Research Institute of Genetics and Selection of Industrial Microorganisms
6. Vavilov Institute of General Genetics
7. Cancer Research Center
Edição: Volume 51, Nº 1 (2017)
Páginas: 61-71
Seção: Molecular Cell Biology
URL: https://journals.rcsi.science/0026-8933/article/view/162931
DOI: https://doi.org/10.1134/S0026893316060169
ID: 162931

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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 r_s 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 (r_s 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.

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epigenetic mechanisms, expression regulation, methylation, renal cell carcinoma, chromosome 3 genes, microRNA, miR-129-2

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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

Texto integral

Resumo

Palavras-chave

Sobre autores

I. Pronina

E. Klimov

A. Burdennyy

E. Beresneva

M. Fridman

V. Ermilova

T. Kazubskaya

A. Karpukhin

E. Braga

V. Loginov

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