Article Text

Download PDFPDF
Extended effects of human papillomavirus 16 E6-specific short hairpin RNA on cervical carcinoma cells
  1. L. Bai*,
  2. L. Wei*,
  3. J. Wang*,
  4. X. Li* and
  5. P. He
  1. *Department of Obstetrics and Gynecology, Beijing, China
  2. Department of Molecular Biology, Peking University People's Hospital, Beijing, China
  1. Address correspondence and reprint requests to: Lihui Wei, MD, Department of Obstetrics and Gynecology, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing 100044, China. Email: weilh19{at}china.com

Abstract

Most cervical carcinomas express high-risk human papillomavirus (HPV) E6 and E7 oncogenes. Small interfering RNA can mediate sequence-specific inhibition of gene expression in mammalian cells. To find a most effective short hairpin RNA (shRNA) for HPV16 E6 messenger RNA (mRNA) and investigate the extended effects of the HPV16 E6 shRNA on cervical carcinoma cells, we stably transfected SiHa cells with four shRNA expression vectors (E6A–D). HPV16 E6A shRNA was found to be the most efficient in our study, which caused the reduction of HPV16 E6 mRNA to 10% in SiHa cells but did not reduce HPV18 E6 mRNA expression in HeLa cells. We subsequently demonstrated that E6A could stably express shRNA and effectively reduce HPV16 E6 and E7 viral genes expression in SiHa cells for more than 4 months. After E6 and E7 repression, there was a dramatic accumulation of p53, p21, and hypophosphorylated pRb proteins in cells. Furthermore, cell proliferation, colony formation ability, tumorigenicity, and in vitro cell invasive capability were suppressed substantially in E6A-transfected cells. These results suggest that the use of shRNA expression vector may be a potential approach for the treatment of persistent HPV infection and HPV-positive cervical carcinoma.

  • cervical carcinoma
  • human papillomavirus
  • short hairpin RNA

Statistics from Altmetric.com

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.