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)...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2006-12, Vol.103 (49), p.18680-18684
Main Authors: Wang, Clifford L., Wang, Bruce B., Bartha, Gábor, Li, Lauri, Channa, Namitha, Klinger, Mark, Killeen, Nigel, Wabl, Matthias
Format: Article
Language:English
Subjects:
Animals
Biological Sciences
DNA
Fibroblasts
Gene expression
Gene Expression Regulation, Neoplastic
Gene Expression Regulation, Viral
Genes
Infections
Leukemia
Leukemia Virus, Murine - genetics
Leukemia, Experimental - genetics
Leukemia, Experimental - virology
Lymphoma
Male
Mice
Mice, Inbred BALB C
MicroRNA
MicroRNAs - metabolism
Murine leukemia virus
Oncogenes
Oncogenes - physiology
Polymerase chain reaction
Proviruses
Proviruses - genetics
Retroviridae Infections - genetics
Retroviridae Infections - virology
RNA
RNA, Neoplasm - metabolism
RNA, Viral - metabolism
Rodents
Tumor Virus Infections - genetics
Tumor Virus Infections - virology
Tumors
Virus Integration - physiology
Viruses
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0609030103