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- Title
Identification of cellular targets for the human papillomavirus E6 and E7 oncogenes by RNA interference and transcriptome analyses.
- Authors
Kuner, Ruprecht; Vogt, Markus; Sultmann, Holger; Buness, Andreas; Dymalla, Susanne; Bulkescher, Julia; Fellmann, Mark; Butz, Karin; Poustka, Annemarie; Hoppe-Seyler, Felix
- Abstract
Specific types of human papillomaviruses (HPVs) cause cervical cancer, the second most common tumor in women worldwide. Both cellular transformation and the maintenance of the oncogenic phenotype of HPV-positive 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 transcriptome 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 C-MYC-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.
- Subjects
PAPILLOMAVIRUSES; ONCOGENIC DNA viruses; MEIOSIS; CERVICAL cancer; CANCER in women; WOMEN'S health
- Publication
Journal of Molecular Medicine, 2007, Vol 85, Issue 11, p1253
- ISSN
0946-2716
- Publication type
Article
- DOI
10.1007/s00109-007-0230-1