Discordant correlation of DNA methylation in different regions of the CARMN (MIR143HG) gene with expression of the miR-143/145 cluster in carotid atherosclerotic plaques

Abstract

Impaired stability of carotid artery atherosclerotic plaques (CAAP) is associated with changes in miR-143/145 expression. In some tissues, the miR-143/145 expression is regulated by CARMN (MIR143HG) promoter methylation, however, it is possible that methylation in the promoters of the MIR143 and MIR145 genes, which are located in the CARMN gene body, may be influenced. As a rule, there is a negative correlation between methylation in promoter regions of genes and their expression. The aim of our study was to analyze the association of miR-143/145 expression with the methylation level of CpG sites in CARMN gene in CAAPs. DNA and microRNA for analysis were extracted from CAAPs of patients with advanced carotid atherosclerosis (n=14). DNA methylation analysis was performed by MethylChip, and microRNA expression was analyzed using the microRNA-seq method. We revealed an inverse correlation of miR-145-3p and miR-143-3p expression with methylation of cg01726320, cg01558401 and cg26585864 in the CARMN promoter and a direct correlation with methylation of cg04317047, cg16684117 and cg21242144 in the CARMN gene body and in the MIR143 and MIR145 promoters. These results suggest an important role of CARMN promoter methylation in the regulation of miR-143/145 expression in carotid atherosclerosis.