siRNA targeting of the viral E6 oncogene efficiently kills human papillomavirus-positive cancer cells

Oncogene. 2003 Sep 4;22(38):5938-45. doi: 10.1038/sj.onc.1206894.


The targeted inhibition of antiapoptotic factors in tumour cells may provide a rational approach towards the development of novel anticancer therapies. Using human papillomavirus (HPV)-transformed cells as a model system, we investigated if RNA interference (RNAi)-mediated gene silencing can be employed in order to overcome the apoptosis resistance of cancer cells. We found that both vector-borne and synthetic small interfering (si)RNAs, specifically directed against the antiapoptotic HPV E6 oncogene, restored dormant tumour suppressor pathways in HPV-positive cancer cells that are otherwise inactive in the presence of E6. This ultimately resulted in massive apoptotic cell death, selectively in HPV-positive tumour cells. These findings show that RNAi provides a powerful molecular strategy to inactivate intracellular E6 function efficiently. Moreover, they define E6 as a most promising therapeutic target to eliminate HPV-positive tumour cells specifically by RNAi. Thus, by sequence-specific targeting of antiapoptotic genes, siRNAs may be developed into novel therapeutics that can efficiently correct the apoptosis deficiency of cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / genetics
  • DNA-Binding Proteins*
  • Genetic Therapy / methods
  • HeLa Cells / drug effects
  • HeLa Cells / virology
  • Humans
  • Oncogene Proteins, Viral / drug effects
  • Oncogene Proteins, Viral / genetics*
  • RNA, Small Interfering / genetics*
  • RNA, Small Interfering / pharmacology
  • Retinoblastoma Protein / genetics
  • Retinoblastoma Protein / metabolism
  • Transfection
  • Tumor Cells, Cultured
  • Tumor Stem Cell Assay
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism


  • DNA-Binding Proteins
  • E6 protein, Human papillomavirus type 18
  • E7 protein, Human papillomavirus type 18
  • Oncogene Proteins, Viral
  • RNA, Small Interfering
  • Retinoblastoma Protein
  • Tumor Suppressor Protein p53