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Genome-Wide Methylation Profiling in Canine Mammary Tumor Reveals miRNA Candidates Associated with Human Breast Cancer

Department of Biochemistry, BK21 Plus and Research Institute for Veterinary Science, School of Veterinary Medicine, Seoul National University, Seoul 08826, Korea
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Cancers 2019, 11(10), 1466; https://doi.org/10.3390/cancers11101466
Received: 21 June 2019 / Revised: 27 August 2019 / Accepted: 18 September 2019 / Published: 29 September 2019
Genome-wide methylation profiling is used in breast cancer (BC) studies, because DNA methylation is a crucial epigenetic regulator of gene expression, involved in many diseases including BC. We investigated genome-wide methylation profiles in both canine mammary tumor (CMT) tissues and peripheral blood mononuclear cells (PBMCs) using reduced representation bisulfite sequencing (RRBS) and found unique CMT-enriched methylation signatures. A total of 2.2–4.2 million cytosine–phosphate–guanine (CpG) sites were analyzed in both CMT tissues and PBMCs, which included 40,000 and 28,000 differentially methylated regions (DMRs) associated with 341 and 247 promoters of differentially methylated genes (DMGs) in CMT tissues and PBMCs, respectively. Genes related to apoptosis and ion transmembrane transport were hypermethylated, but cell proliferation and oncogene were hypomethylated in tumor tissues. Gene ontology analysis using DMGs in PBMCs revealed significant methylation changes in the subset of immune cells and host defense system-related genes, especially chemokine signaling pathway-related genes. Moreover, a number of CMT tissue-enriched DMRs were identified from the promoter regions of various microRNAs (miRNAs), including cfa-mir-96 and cfa-mir-149, which were reported as cancer-associated miRNAs in humans. We also identified novel miRNAs associated with CMT which can be candidates for new miRNAs associated with human BC. This study may provide new insight for a better understanding of aberrant methylation associated with both human BC and CMT, as well as possible targets for methylation-based BC diagnostic markers. View Full-Text
Keywords: DNA methylation; canine mammary tumor; miRNA in cancer DNA methylation; canine mammary tumor; miRNA in cancer
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Jeong, S.-J.; Lee, K.-H.; Nam, A.-R.; Cho, J.-Y. Genome-Wide Methylation Profiling in Canine Mammary Tumor Reveals miRNA Candidates Associated with Human Breast Cancer. Cancers 2019, 11, 1466.

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