Роль метилирования генов микроРНК в патогенезе первичных опухолей почки и легкого

V I Loginov; S V Rykov; E V Beresneva; V V Hokonova; D S Hodyrev; I V Pronina; A M Burdennyy; T P Kazubskaya; E A Braga

V I Loginov Institute of General Pathology and Pathophysiology, Russian Academy of Sciences, Moscow 125315
S V Rykov Scientific Center of Russian Federation Institute for Genetics and Selection of Industrial Microorganisms, Moscow
E V Beresneva Center of Russian Federation Institute for Genetics and Selection of Industrial Microorganisms, Moscow
V V Hokonova Institute of General Pathology and Pathophysiology, Russian Academy of Sciences, Moscow 125315
D S Hodyrev FSBSI «Federal Clinical Scientific Centre of special medical help types and medical technologies» FMBA of Russia, Moscow
I V Pronina Research Centre for Medical Genetics, Moscow
A M Burdennyy Institute of General Pathology and Pathophysiology, Russian Academy of Sciences, Moscow 125315
T P Kazubskaya Blokhin Cancer Research Center, Moscow
E A Braga Institute of General Pathology and Pathophysiology, Russian Academy of Sciences, Moscow 125315

Keywords: microRNA genes, methylation, methylation-specific PCR, non-small cell lung cancer (NSCLC), clear cell renal cell carcinoma (ccRCC)

Abstract

MicroRNAs play important role in the protein coding genes expression regulation and are involved in the development of cancer. One of the miRNA gene expression regulation mechanisms is their promoter CpG islands methylation. We investigated CpG-island methylation of eight miRNA genes (MIR-9-1/3, MIR-34b/c, MIR-124a-1/2/3, MIR-129-2) in a representative selected samples of primary kidney and lung tumors (46 cases of each type) using methylation-specific PCR. Methylation of four genes — MIR-124a-1/2/3 and MIR-129-2 in the kidney tumors and MIR-129-2 in lung tumors was studied by us for the first time. It was shown that frequency of methylation of these genes in the studied NSCLC and ccRCC tumor samples was varied from 41% to 67% and was significantly higher than in normal tissue biopsy samples (r < 0.05, Fischer). A significant increase in the frequency of methylation of MIR-124a-3 and MIR-34b/c genes observed in NSCLC was rather different in various histological types — squamous cell carcinoma (SCC) and adenocarcinoma (AC). A significant increase of methylation frequency of MIR-124a-2 and the MIR-129-2 genes was also found in SCC (in difference of AC), which was shown for the first time and can be used in the differential diagnosis of SCC and AK. Correlations of methylation frequencies of several miRNA genes with tumor progression of ccRCC and NSCLC (tumor size, stage, loss of differentiation, metastasis) were revealed here.

Methylation of miRNA genes in the pathogenesis of primary kidney and lung tumors

Abstract