Methylation and expression levels of microRNA-23b/-24-1/-27b, microRNA-30c-1/-30e, microRNA-301a and let-7g are dysregulated in clear cell renal cell carcinoma.

Abstract

Renal cell carcinoma is the most common form of kidney cancer in adults. DNA methylation of regulatory sequences at the genomic level and interaction between microRNAs and the messenger RNAs of target genes at the posttranscriptional level contribute to the dynamic regulation of gene activity. Aberrations in these mechanisms can result in impaired functioning of cell signaling pathways, such as that observed in malignant tumors. We hypothesized that microRNA genes methylation may be associated with renal cancer in patients. We examined methylation levels of 22 microRNA genes in tumor and normal kidney tissue of 30 patients with TNM Stage III clear cell renal cell carcinoma using a pathway-specific real-time polymerase chain reaction array (EpiTect Methyl II PCR Arrays, Qiagen). MicroRNA expression analysis by quantitative polymerase chain reaction was also performed. Significant differences in methylation levels were found in two genes and in two clusters of microRNA genes. MicroRNA-23b/-24-1/-27b, microRNA -30c-1/-30e and let-7g was hypermetylated in clear cell renal cell carcinoma tissue, microRNA -301a was hypomethylated in tumor compared with the adjacent normal tissues. Expression of microRNA-301a, microRNA-23b in the clear cell renal cell carcinoma tissues was significantly overexpressed when compared with the adjacent normal tissues and let-7g was significantly downregulated in tumor. Our results may indicate the contribution of microRNA-301a, microRNA-23b and let-7g in the pathogenesis of renal cancer, but further studies are needed to determine the functional significance of the detected changes.