Human papillomavirus (HPV)-associated carcinogenesis: Identification of putative cellular target genes by RNA interference affecting viral oncogene expression and subsequent transcriptome analysis.

A138

Specific types of human papillomaviruses (HPVs) cause cervical cancer, the second most common tumor in females worldwide. Cellular transformation is linked to expression of the viral E6 and E7 oncogenes. The E6 oncoprotein induces the proteolytic degradation of p53, whereas E7 inactivates the retinoblastoma protein, pRb, and other pocket proteins. We employed the RNA interference (RNAi) technology, in order to inhibit E6 expression alone, or in combination with E7, in HPV-positive HeLa cells. After genome-wide microarray experiments, the set of genes which was affected by RNAi was compared with gene expression data from p53 siRNA-knockdown experiments and with public available from HPV-positive cervical carcinoma tissue. In this meta-analysis, a large accordance was found between the genes affected in our E6/E7 knockdown experiments and genes which were found to be modulated in HPV-positive cervical cancer biopsies. After functional annotation, we were able to confirm the affection of known tumor-relevant processes, like the inhibition of cell cycle arrest and apoptosis, but found also novel molecular aspects of HPV-driven tumorigenesis.