MicroRNA-15b is induced with E2F-controlled genes in HPV-related cancer

Br J Cancer. 2011 Nov 22;105(11):1719-25. doi: 10.1038/bjc.2011.457. Epub 2011 Nov 1.


Background: MicroRNAs (miRNAs) are important regulators of cellular processes and are found to be deregulated in many cancers. We here analysed the miRNA expression in anal carcinomas. In a previous study, we found that our anal carcinoma tumours were divided into two groups based on the expression of E2F-regulated genes. Therefore, we searched for miRNAs that could reproduce this grouping.

Methods: A global screen of the miRNA population was performed using real-time quantitative PCR (RT-qPCR) array methods and differentially expressed miRNAs were identified. Real-time-qPCR was used to verify the expression levels of selected miRNAs and genes in a larger collection of biopsies. A siRNA-mediated knockdown of human papilloma virus (HPV)16 E7 in a cervical cell line was performed to assess the effect of E7 on miR-15b.

Results: The grouping of tumours into two groups based on the expression of E2F-controlled genes was confirmed in a larger collection of anal carcinoma tumours. The expression of miR-15b was shown to be highly correlated with that of five selected E2F-induced genes (CCNA2, CCNB1, CCNB2, MSH6 and MCM7). A knockdown of HPV16 E7 resulted in decreased levels of miR-15b in Ca Ski cells.

Conclusion: MiR-15b expression correlates with E2F-regulated genes in anal carcinoma and appears to be part of the E2F-regulatory network.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anus Neoplasms / genetics*
  • Anus Neoplasms / metabolism
  • Anus Neoplasms / virology*
  • Cell Line, Tumor
  • Cyclin E / genetics
  • Cyclin E / metabolism
  • E2F Transcription Factors / genetics*
  • E2F Transcription Factors / metabolism
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques / methods
  • Genetic Testing / methods
  • Human papillomavirus 16 / genetics*
  • Human papillomavirus 16 / metabolism
  • Human papillomavirus 18 / genetics
  • Human papillomavirus 18 / metabolism
  • Humans
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Papillomavirus E7 Proteins / genetics*
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction / methods


  • Cyclin E
  • E2F Transcription Factors
  • MIRN15 microRNA, human
  • MicroRNAs
  • Papillomavirus E7 Proteins
  • RNA, Messenger
  • oncogene protein E7, Human papillomavirus type 16