title: [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].
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.
authors.affiliation: Research Centre of Medical Genetics, Moscow, 115478 Russia.|Institute of General Pathology and Pathophysiology, Moscow, 125315 Russia.|zolly_sten@mail.ru.
authors.forename: I V
authors.initials: IV
authors.lastname: Pronina
authors.affiliation: Biological Faculty, Moscow State University, Moscow, 119234 Russia.
authors.forename: E A
authors.initials: EA
authors.lastname: Klimov
authors.affiliation: Institute of General Pathology and Pathophysiology, Moscow, 125315 Russia.|Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Moscow, 119334 Russia.
authors.forename: A M
authors.initials: AM
authors.lastname: Burdennyy
authors.affiliation: State Research Institute of Genetics and Selection of Industrial Microorganisms, Moscow, 117545 Russia.
authors.forename: E V
authors.initials: EV
authors.lastname: Beresneva
authors.affiliation: Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, 117971 Russia.
authors.forename: M V
authors.initials: MV
authors.lastname: Fridman
authors.affiliation: Blokhin Cancer Research Center, Moscow, 115478 Russia.
authors.forename: V D
authors.initials: VD
authors.lastname: Ermilova
authors.affiliation: Blokhin Cancer Research Center, Moscow, 115478 Russia.
authors.forename: T P
authors.initials: TP
authors.lastname: Kazubskaya
authors.affiliation: Research Centre of Medical Genetics, Moscow, 115478 Russia.
authors.forename: A V
authors.initials: AV
authors.lastname: Karpukhin
authors.affiliation: Research Centre of Medical Genetics, Moscow, 115478 Russia.|Institute of General Pathology and Pathophysiology, Moscow, 125315 Russia.
authors.forename: E A
authors.initials: EA
authors.lastname: Braga
authors.affiliation: Research Centre of Medical Genetics, Moscow, 115478 Russia.|Institute of General Pathology and Pathophysiology, Moscow, 125315 Russia.|loginov7w@gmail.com.
authors.forename: V I
authors.initials: VI
authors.lastname: Loginov
mesh_terms: D002292:Carcinoma, Renal Cell / Q000235:genetics*; D045744:Cell Line, Tumor; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D011401:Promoter Regions, Genetic
chemical_list: C541874:MIRN92 microRNA, human; D035683:MicroRNAs; C541915:Mirn129 microRNA, human
keywords: chromosome 3  genes; epigenetic mechanisms; expression regulation; methylation; miR-129-2; microRNA; renal cell carcinoma