Genome-wide DNA methylation and expression patterns of microRNAs in relation to breast cancer subtypes among American women of African and European ancestry [methylation array]

ABSTRACT: We reAggressive high-grade, estrogen receptor negative (ER-) breast cancer is more common among American women of African ancestry (AA) than those of European ancestry (EA). The reasons remain largely unknown. Epigenetic mechanisms, particularly DNA methylation and altered microRNA (miRNA) expression, may contribute to racial differences in breast cancer. However, the characterization of this epigenetic modification in relation to ER+ and ER- breast cancer, and its functional role in the regulation of miRNA expression remains to be investigated, especially among high risk AA women. In this study, we evaluated methylation patterns of miRNA genes and their effect on miRNA expression in breast tumors from both AA and EA women. The genome-wide methylation screen identified a number of differentially methylated loci (DML) between ER- and ER+ tumor subtypes in tumors from both races, or specific to AA or EA women. Integrated analysis of DNA methylation and miRNA expression further identified certain DMLs whose methylation levels were significantly correlated with the expression of relevant miRNAs, such as multiple CpGs highly correlated with miR-190b and miR-135b. In summary, our results suggest that DNA methylation patterns in miRNA encoding genes differ between breast cancers according to cancer subtype and race, and that this altered methylation may affect miRNA expression. Further pathway analysis identified their potential role in modulating cancer-related key biological processes. These findings shed light on the epigenetic regulation of miRNA expression and provide insights into the relations of clinical-relevant miRNAs to their target genes and to serve as potential preventative and therapeutic targets. port the application of single-molecule-based sequencing technology for high-throughput profiling of histone modifications in mammalian cells. By obtaining over four billion bases of sequence from chromatin immunoprecipitated DNA, we generated genome-wide chromatin-state maps of mouse embryonic stem cells, neural progenitor cells and embryonic fibroblasts. We find that lysine 4 and lysine 27 trimethylation effectively discriminates genes that are expressed, poised for expression, or stably repressed, and therefore reflect cell state and lineage potential. Lysine 36 trimethylation marks primary coding and non-coding transcripts, facilitating gene annotation. Trimethylation of lysine 9 and lysine 20 is detected at satellite, telomeric and active long-terminal repeats, and can spread into proximal unique sequences. Lysine 4 and lysine 9 trimethylation marks imprinting control regions. Finally, we show that chromatin state can be read in an allele-specific manner by using single nucleotide polymorphisms. This study provides a framework for the application of comprehensive chromatin profiling towards characterization of diverse mammalian cell populations.

ORGANISM(S): Homo sapiens

PROVIDER: GSE156968 | GEO | 2021/01/01

REPOSITORIES: GEO