Genome‐wide DNA methylation analysis by MethylRad and the transcriptome profiles reveal the potential cancer‐related lncRNAs in colon cancer

Abstract

Abstract Colon cancer (CC) is characterized by global aberrant DNA methylation that may affect gene expression and genomic stability. A series of studies have demonstrated that DNA methylation could regulate the expressions of not only protein‐coding genes but also ncRNAs. However, the regulatory role of lncRNA genes methylaton in CC remains largely unknown. In the present study, we systemically characterize the profile of DNA methylation, especially the aberrant methylation of lncRNAs genes using MethylRAD technology. A total of 132 999 CCGG/8487 CCWGG sites were identified as differentially methylated sites (DMSs), which were mainly located on the introns and intergenic elements. Moreover, 1,359 CCGG/1,052 CCWGG differentially methylated genes (DMGs) were screened. Our results demonstrated that aberrant methylation of lncRNA genes occurred most frequently, accounting for 37.5% and 44.3% in CCGG and CCWGG DMGs respectively. In addition, 963 lncRNA DMGs were co‐analyzed with 1328 differentially expressed lncRNAs which were identified from TCGA database. We found that 15 lncRNAs might be CC‐related lncRNAs. ZNF667‐AS1 and MAFA‐AS1 were down‐regulated in CC, which might be silenced by hypermethylation. Besides, 13 lncRNAs were hypomethylated and up‐regulated in CC. Moreover, our results validated the expression and methylation level of CC‐related lncRNAs by RT‐qPCR and pyrosequencing assay. In conclusion, we performed a genome‐wide DNA methylation analysis by MethylRAD to acquire both CCGG and CCWGG DMSs and DMGs in CC. The results screened lncRNA DMSs as potential biomarkers and identified 15 lncRNAs as CC‐related lncRNAs. This study provided novel therapy targets and valuable insights into molecular mechanism in tumorigenesis and development of CC.

Keywords

• Bioinformatic analysis
• Colon cancer
• lncRNA gene methylation
• MethylRAD