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      Activation of an oncogenic microRNA cistron by provirus integration.

      Proceedings of the National Academy of Sciences of the United States of America
      Animals, Gene Expression Regulation, Neoplastic, Gene Expression Regulation, Viral, Leukemia Virus, Murine, genetics, Leukemia, Experimental, virology, Male, Mice, Mice, Inbred BALB C, MicroRNAs, metabolism, Oncogenes, physiology, Proviruses, RNA, Neoplasm, RNA, Viral, Retroviridae Infections, Tumor Virus Infections, Virus Integration

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          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.

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