Computational epigenetic landscape analysis reveals association of CACNA1G-AS1, F11-AS1, NNT-AS1, and MSC-AS1 lncRNAs in prostate cancer progression through aberrant methylation

Abstract

Aberrant expression of long non-coding RNAs (lncRNAs), caused by alterations in DNA methylation, is a driving factor in several cancers. Interplay between lncRNAs’ aberrant methylation and expression in prostate cancer (PC) progression still remains largely elusive. Therefore, this study characterized the genome-wide epigenetic landscape and expression profiles of lncRNAs and their clinical impact by integrating multi-omics data implementing bioinformatics approaches. We identified 62 differentially methylated CpG-sites (DMCs) and 199 differentially expressed lncRNAs (DElncRNAs), where 32 DElncRNAs contain 32 corresponding DMCs within promoter regions. Significant negative correlation was observed between 8 DElncRNAs-DMCs pairs. 3 (cg23614229, cg23957912, and cg11052780) DMCs and 4 (CACNA1G-AS1, F11-AS1, NNT-AS1, and MSC-AS1) DElncRNAs were identified as high-risk factors for poor prognosis of PC patients. Overexpression of hypo-methylated CACNA1G-AS1, F11-AS1, and NNT-AS1 and down-regulation of hyper-methylated MSC-AS1 significantly lower the survival of PC patients and could be a potential prognostic and therapeutic biomarker. These DElncRNAs were found to be associated with several molecular functions whose deregulation can lead to cancer. Involvement of these epigenetically deregulated DElncRNAs in cancer-related biological processes was also noticed. These findings provide new insights into the understanding of lncRNA regulation by aberrant DNA methylation which will help to clarify the epigenetic mechanisms underlying PC.