PDF(Pubmed)
Abstract：
Ubiquitin-like with PHD and RING finger domains 1 (UHRF1) is an epigenetic regulator that plays critical roles in tumours. However, the DNA methylation alteration patterns driven by UHRF1 and the related differentially expressed tumour-related genes remain unclear. In this study, a UHRF1-shRNA MCF-7 cell line was constructed, and whole-genome bisulfite sequencing and RNA sequencing were performed. The DNA methylation alteration landscape was elucidated, and DNA methylation-altered regions (DMRs) were found to be distributed in both gene bodies and adjacent regions. The DMRs were annotated and categorized into 488 hypermethylated/1696 hypomethylated promoters and 1149 hypermethylated/5501 hypomethylated gene bodies. Through an integrated analysis with the RNA sequencing data, 217 methylation-regulated upregulated genes and 288 downregulated genes were identified, and these genes were primarily enriched in nervous system development and cancer signalling pathways. Further analysis revealed 21 downregulated oncogenes and 15 upregulated TSGs. We also showed that UHRF1 silencing inhibited cell proliferation and migration and suppressed tumour growth in vivo. Our study suggested that UHRF1 and the oncogenes or TSGs it regulates might serve as biomarkers and targets for breast cancer treatment.
摘要：
具有PHD和环指结构域1(UHRF1)的泛素样是在肿瘤中起关键作用的表观遗传调节因子。然而,UHRF1驱动的DNA甲基化改变模式和相关差异表达的肿瘤相关基因仍不清楚.在这项研究中,构建了UHRF1-shRNAMCF-7细胞系，进行了全基因组亚硫酸氢盐测序和RNA测序。阐明了DNA甲基化改变的前景，发现DNA甲基化改变区（DMRs）分布在基因体和相邻区域。对DMR进行注释并分类为488个高甲基化/1696个低甲基化启动子和1149个高甲基化/5501个低甲基化基因体。通过与RNA测序数据的综合分析，确定了217个甲基化调节的上调基因和288个下调基因，这些基因主要富集在神经系统发育和癌症信号通路中。进一步分析显示21个下调的癌基因和15个上调的TSG。我们还表明，UHRF1沉默在体内抑制细胞增殖和迁移，并抑制肿瘤生长。我们的研究表明，UHRF1及其调节的癌基因或TSG可能作为乳腺癌治疗的生物标志物和靶标。
