WITHDRAWN: Genome-Wide DNA Methylome and Whole-Transcriptome Landscapes of Spontaneous Intraductal Papilloma in Tree Shrews (Tupaia Belangeri)

Abstract

BackgroundBreast intraductal papilloma (IP) is mainly caused by the abnormal proliferation of ductal epithelial cells. Tree shrews are a potential animal model for studying breast tumours. However, little is known about the transcriptome and DNA methylome landscapes of breast IP in tree shrews. In this work, we performed whole-genome DNA methylation and transcriptome analyses of breast IPs and normal mammary glands in tree shrews.ResultsDNA methylation profiles with a single-base resolution were generated via whole-genome bisulphate sequencing (WGBS) in both the IP and Control groups of tree shrews. This provided a genome-wide perspective regarding the epigenetic regulation of protein-coding genes in breast IP in tree shrews. The methylation levels at CG sites were considerably higher than those at CHG and CHH sites, and methylation levels were highest in gene body regions. We identified 3486, 82 and 361 differentially methylated regions (DMRs) in CG, CHG, and CHH contexts, respectively, and 701 differentially methylated genes (DMGs) were found. Furthermore, transcriptomic analysis identified 62 differentially expressed genes (DEGs), 50 long noncoding RNAs (lncRNAs), and 32 circular RNAs (circRNAs) in IPs compared with normal mammary glands. Correlation analysis between the DNA methylation and transcriptome data showed that 25 DMGs were also DEGs, among which the expression levels of 9 genes were negatively correlated with methylation levels in gene body regions. Importantly, integrated analysis identified three genes, PDZK1, ATP2B4 and LCP1, that could be used as candidates for further studying breast IP in tree shrews.ConclusionsOverall, this research provides the comprehensive landscape of the transcriptome and DNA methylome of spontaneous IP in tree shrews and highlights candidate genes for eliciting tumorigenesis. These results contribute to the application of tree shrews as an animal model of breast tumours.