UHRF1(ubiquitin-like with PHD and Ring finger domains 1)是一种维持DNA甲基化修饰的表观遗传调控因子,在胚胎发育和肿瘤发生发展及预后中发挥重要作用.研究鉴定了受UHRF1 调控的差异表达基因,并对基因参与的细胞功能、代谢途径和疾病相关通路进行分析.提取UHRF1 敲低细胞(MCF-7/shRNA-UHRF1)和对照组细胞(MCF-7/shRNA-Scramble)的RNA进行RNA-Seq测序,利用DESeq2 软件对差异表达基因进行鉴定,并通过qRT-PCR对部分基因进行验证.利用Gene ontology(GO)功能聚类、Kyoto Encylopedia of Genes and Genomes(KEGG)代谢通路富集分析、Disease ontology(DO)疾病聚类分析等方法分析差异基因的潜在功能.研究共鉴定出 2926 个受UHRF1 调控的差异表达基因,与对照组相比,shRNA-UHRF1 细胞中有 1453 个基因下调表达,1473 个基因上调表达.GO和KEGG分析显示,差异表达基因主要参与细胞代谢、免疫调节、信号传导、心血管疾病和肿瘤发生等.DO功能富集分析显示这些基因参与癌症和神经性疾病.研究结果表明,表观遗传调控因子UHRF1 介导的DNA甲基化可在转录水平上调控基因的差异表达,为UHRF1 参与调控相关信号通路提供数据支持.
Identification and analysis of differential expression genes regulated by UHRF1 in breast cancer cells
Ubiquitin-like with PHD and Ring finger domains 1(UHRF1)is an epigenetic regulator that maintains DNA methylation modification and plays critical roles in embryonic development,tumor progress and prognosis.In this study,the differential expression genes regulated by UHRF1 was identified,and the associated cell functions,metabolic pathways,and related diseases these genes in-volved were investigated.Total RNA extracted from UHRF1 knockdown cells(MCF-7/shRNA-UHRF1)or scramble cells(MCF-7/shRNA-Scramble)as a control was subjected to RNA-Seq analysis,then the differential expression genes were screened by using DESeq2 software and partially validated by qRT-PCR.Gene ontology(GO),Kyoto Encylopedia of Genes and Genomes(KEGG)and Disease ontology(DO)analyses were employed to investigate the potential biological functions of these genes.The results showed that a total of 2926 genes expression were regulated by UHRF1.Among them,1453 genes were down-regulated and 1473 genes were up-regulated by UHRF1 knockdown.GO and KEGG analysis showed that these genes were primarily enriched in cell metabolism,im-mune regulation,signal transduction,cardiovascular disease and tumorigenesis.DO analysis showed that they were mainly involved in cancer and neurological diseases.These results suggested that DNA methylation mediated by the epigenetic regulatory factor UHRF1 can regulate the differential expression of genes at the transcriptional level,providing data support for the participation of UHRF1 in the regulation of relevant signaling pathways.
万方数据
维普
