DNA methylation patterns in breast cancer are associated with, and may influence, disease outcome, including survival, but questions still remain regarding the regulation of DNA methylation activity. Previous research has shown that proteins associated with DNA methylation, such as the DNA methyltransferase (DNMT) family and methyl-binding domain (MBD) proteins, form complexes among themselves, as well as with histone-modification machinery(1), and that these proteins contain RNA binding regions(2). To date however, only one long non-coding RNA (lncRNA), ecCEPBA, has been associated with a DNA methylation proteins. The ecCEPBA lncRNA, produced from the CEPBA gene, associates with DNMT1, and is critical for regulation of DNA methylation in breast and other cancers(3, 4).
There is little information regarding other lncRNAs that are associated with, or involved in, regulation of other elements of the DNA methylation machinery or with active DNA demethylation. We aim to explore the role of lncRNAs associated with DNA methylation in breast cancer further, by using publically available datasets to look for patterns of expression of proteins associated with DNA methylation, and also to examine methylation-associated gene expression clusters for various clinical characteristics, including molecular tumour classification, and disease survival. We then analyzed mRNA data from the same database using weighted gene co-expression network (WGCNA) analysis to develop a candidate list of potentially associated lncRNAs, which may be further experimentally validated. Results of this analysis will be presented.
This analysis will shed further light on the interaction between lncRNAs and the epigenetic machinery involved in DNA methylation, in the context of breast cancer.