Identification of cellular targets for the human papillomavirus E6 and E7 oncogenes by RNA interference and transcriptome analyses
Identification of cellular targets for the human papillomavirus E6 and E7 oncogenes by RNA interference and transcriptome analyses
复制标题
DOI：
10.1007/s00109-007-0230-1
复制
发表时间：
2007-11-01
影响因子：
4.7
通讯作者：
Hoppe-Seyler, Felix
中科院分区：
文献类型：
--
作者：
Kuner, Ruprecht;Vogt, Markus;Hoppe-Seyler, Felix
特定类型的人类乳头状病毒（hpv）导致宫颈癌，这是世界范围内女性第二大常见肿瘤。hpv阳性肿瘤细胞的细胞转化和致癌表型的维持都与病毒E6和E7癌基因的表达有关。为了确定病毒致癌基因的下游细胞靶基因，我们通过RNA干扰（RNAi）沉默hpv阳性HeLa细胞内源性E6和E7的表达。随后，我们通过全基因组微阵列分析评估了细胞转录的变化。我们鉴定出648个基因，在E6/E7表达受到抑制后，这些基因或下调（360个）或上调（288个）。这些基因中的很大一部分参与肿瘤相关过程，如细胞凋亡控制、细胞周期调节或纺锤体形成。其他可能代表了HPV癌基因的新细胞靶点，例如参与RNA加工和剪接的一大组cmyc相关基因。与已发表的微阵列数据进行比较，发现HeLa细胞中被rnai介导的E6/E7沉默所抑制的基因与hpv阳性宫颈癌活检中报道的上调基因之间存在实质性的一致性。
Specific types of hurnan papillornaviruses (HPVs) cause cervical cancer, the second most common tumor in women worldwide. Both cellular transformation and the maintenance of the oncogenic phenotype of HPVpositive tumor cells are linked to the expression of the viral E6 and E7 oncogenes. To identify downstream cellular target genes for the viral oncogenes, we silenced endogenous E6 and E7 expression in HPV-positive HeLa cells by RNA interference (RNAi). Subsequently, we assessed changes of the cellular transcriptorne by genome-wide microarray analysis. We identified 648 genes, which were either downregulated (360 genes) or upregulated (288 genes), upon inhibition of E6/E7 expression. A large fraction of these genes is involved in tumor-relevant processes, such as apoptosis control, cell cycle regulation, or spindle formation. Others may represent novel cellular targets for the HPV oncogenes, such as a large group of CMYC-associated genes involved in RNA processing and splicing. Comparison with published microarray data revealed a substantial concordance between the genes repressed by RNAi-mediated E6/E7 silencing in HeLa cells and genes reported to be upregulated in HPV-positive cervical cancer biopsies.