Induction of cell death in human papillomavirus 18-positive cervical cancer cells by E6 siRNA

K. Yamato, J. Fen, H. Kobuchi, Y. Nasu, T. Yamada, T. Nishihara, Y. Ikeda, M. Kizaki, M. Yoshinouchi

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Human cervical cancer is caused by high-risk types of human papillomavirus (HPV) such as HPV16 and HPV18, which possess the E6 and E7 oncogenes, whose concurrent expression is a prerequisite for cancer development and maintaining malignant phenotypes. Silencing these oncogenes is considered to be applicable in molecular therapies of human cervical cancer. However, it remains to be determined whether E6, E7, or both should be silenced to obtain most efficient antitumor activity by an HPV small-interfering RNA (siRNA). Herein, we report two types of siRNAs targeting HPV18 E6, that exerted a negative growth effect on HPV18-positive cervical cancer cells (HeLa and SW756), in part, inducing cell death. One siRNA (Ex-18E6), designed to target both E6-E7 mRNA and its splicing variant, E6*I-E7 mRNA, efficiently knocked down both E6 and E7 expression. The other (Sp-18E6), designed to specifically target E6-E7 mRNA but not E6*I-E7 mRNA, suppressed E6 to a similar level as Ex-18E6; however, it less efficiently inhibited E7 as compared to Ex-18E6. Although both siRNAs induced cell death, Sp-18E6 siRNA induced more prominent cell death than Ex-18E6. Our results suggest that E6-specific suppression may induce more potent anticancer activity than simultaneous E6 and E7 suppression, and that E6-specific targeting is a promising strategy for siRNA-based therapy for HPV-positive cervical cancer.

Original languageEnglish
Pages (from-to)234-241
Number of pages8
JournalCancer Gene Therapy
Volume13
Issue number3
DOIs
Publication statusPublished - 2006 Mar

Fingerprint

Human papillomavirus 18
Uterine Cervical Neoplasms
Small Interfering RNA
Cell Death
Messenger RNA
Oncogenes
HeLa Cells
Human Activities
Phenotype
Therapeutics
Growth
Neoplasms

Keywords

  • Cell growth
  • Cervical cancer
  • E6
  • Human papillomavirus 18
  • RNA interference
  • siRNA

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Yamato, K., Fen, J., Kobuchi, H., Nasu, Y., Yamada, T., Nishihara, T., ... Yoshinouchi, M. (2006). Induction of cell death in human papillomavirus 18-positive cervical cancer cells by E6 siRNA. Cancer Gene Therapy, 13(3), 234-241. https://doi.org/10.1038/sj.cgt.7700891

Induction of cell death in human papillomavirus 18-positive cervical cancer cells by E6 siRNA. / Yamato, K.; Fen, J.; Kobuchi, H.; Nasu, Y.; Yamada, T.; Nishihara, T.; Ikeda, Y.; Kizaki, M.; Yoshinouchi, M.

In: Cancer Gene Therapy, Vol. 13, No. 3, 03.2006, p. 234-241.

Research output: Contribution to journalArticle

Yamato, K, Fen, J, Kobuchi, H, Nasu, Y, Yamada, T, Nishihara, T, Ikeda, Y, Kizaki, M & Yoshinouchi, M 2006, 'Induction of cell death in human papillomavirus 18-positive cervical cancer cells by E6 siRNA', Cancer Gene Therapy, vol. 13, no. 3, pp. 234-241. https://doi.org/10.1038/sj.cgt.7700891
Yamato, K. ; Fen, J. ; Kobuchi, H. ; Nasu, Y. ; Yamada, T. ; Nishihara, T. ; Ikeda, Y. ; Kizaki, M. ; Yoshinouchi, M. / Induction of cell death in human papillomavirus 18-positive cervical cancer cells by E6 siRNA. In: Cancer Gene Therapy. 2006 ; Vol. 13, No. 3. pp. 234-241.
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