Activation of an oncogenic microRNA cistron by provirus integration.
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.
Wang
Clifford L
CL
Department of Microbiology and Immunology, University of California-San Francisco, San Francisco, CA 94143, USA. cliff.wang@stanford.edu
Wang
Bruce B
BB
Bartha
Gábor
G
Li
Lauri
L
Channa
Namitha
N
Klinger
Mark
M
Killeen
Nigel
N
Wabl
Matthias
M
D000818:Animals; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D009052:Leukemia Virus, Murine / Q000235:genetics*; D007942:Leukemia, Experimental / Q000235:genetics / Q000821:virology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000378:metabolism*; D009857:Oncogenes / Q000502:physiology*; D011533:Proviruses / Q000235:genetics*; D012334:RNA, Neoplasm / Q000378:metabolism*; D012367:RNA, Viral / Q000378:metabolism*; D012192:Retroviridae Infections / Q000235:genetics / Q000821:virology; D014412:Tumor Virus Infections / Q000235:genetics / Q000821:virology; D016662:Virus Integration / Q000502:physiology*
D035683:MicroRNAs; D012334:RNA, Neoplasm; D012367:RNA, Viral