Activation of an oncogenic microRNA cistron by provirus integration

Proc Natl Acad Sci U S A. 2006 Dec 5;103(49):18680-4. doi: 10.1073/pnas.0609030103. Epub 2006 Nov 22.

Abstract

Retroviruses can cause tumors when they integrate near a protooncogene or tumor suppressor gene of the host. We infected >2,500 mice with the SL3-3 murine leukemia virus; in 22 resulting tumors, we found provirus integrations nearby or within the gene that contains the mir-17-92 microRNA (miRNA) cistron. Using quantitative real-time PCR, we showed that expression of miRNA was increased in these tumors, indicating that retroviral infection can induce expression of oncogenic miRNAs. Our results demonstrate that retroviral mutagenesis can be a potent tool for miRNA discovery.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Expression Regulation, Neoplastic
  • Gene Expression Regulation, Viral
  • Leukemia Virus, Murine / genetics*
  • Leukemia, Experimental / genetics
  • Leukemia, Experimental / virology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / metabolism*
  • Oncogenes / physiology*
  • Proviruses / genetics*
  • RNA, Neoplasm / metabolism*
  • RNA, Viral / metabolism*
  • Retroviridae Infections / genetics
  • Retroviridae Infections / virology
  • Tumor Virus Infections / genetics
  • Tumor Virus Infections / virology
  • Virus Integration / physiology*

Substances

  • MicroRNAs
  • RNA, Neoplasm
  • RNA, Viral