Journal
NATURE IMMUNOLOGY
Volume 9, Issue 4, Pages 405-414Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni1575
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Funding
- NIAID NIH HHS [R01 AI064345-02, R01 AI064345-03, R01 AI064345, AI064345, R01 AI064345-01] Funding Source: Medline
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The genomic region encoding the miR-17-92 microRNA ( miRNA) cluster is often amplified in lymphoma and other cancers, and cancer cells carrying this amplification have higher expression of miRNA in this cluster. Retroviral expression of miR-17-92 accelerates c-Myc-induced lymphoma development, but precisely how higher expression of miR-17-92 promotes lymphomagenesis remains unclear. Here we generated mice with higher expression of miR-17-92 in lymphocytes. These mice developed lymphoproliferative disease and autoimmunity and died prematurely. Lymphocytes from these mice showed more proliferation and less activation-induced cell death. The miR-17-92 miRNA suppressed expression of the tumor suppressor PTEN and the proapoptotic protein Bim. This mechanism probably contributed to the lymphoproliferative disease and autoimmunity of miR-17-92-transgenic mice and contributes to lymphoma development in patients with amplifications of the miR-17-92 coding region.
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