Hypermethylation in Ovarian Cancer of Long Non-Coding RNA Genes: <i>HOTAIR</i>, <i>GAS5</i>, <i>LINC00472</i>, <i>LINC00886</i>, <i>TUG1</i>

Abstract

Recently, more and more data have been accumulating indicating the role of long non-coding RNAs (lncRNAs) in the regulation of biological processes in cells, as well as in the mechanisms of cancer development and progression. Aberrant methylation of promoter regions of both protein genes and lncRNA genes can disrupt their expression and functional activity. Using bioinformatics databases, six lncRNA genes (GAS5, HOTAIR, LINC00472, LINC00886, SNHG17 and TUG1) with CpG islands, differentially expressed and presumably hypermethylated in tumors of patients with ovarian cancer (OC) were selected. A statistically significant (p 0.05) increase in the methylation level in tumours was demonstrated in a sample of 93 OC specimens using methylation-specific real-time PCR assay. Moreover, for the genes LINC00472, LINC00886, SNHG17 and TUG1, hypermethylation in OC was detected for the first time. 5 genes (except SNHG17) showed a further increase in methylation levels at a more advanced stage, and 4 genes (except SNHG17 and LINC00886) showed a significant association with metastasis. Using real-time RT-PCR, differential changes in the expression level of the GAS5, HOTAIR, SNHG17 and TUG1 genes and a significant correlation of methylation with expression for the GAS5 gene were shown. Thus, hypermethylation associated with the progression and/or development of OC was detected for six lncRNA genes, which is important for elucidating the epigenetic processes involved in the pathogenesis of OC and can be used as new biomarkers of OC.