Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes.
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.
Pubmed ID: 18327259 RIS Download
Animals | Autoimmune Diseases | Cell Death | Cell Proliferation | Cells, Cultured | Gene Amplification | Gene Expression Regulation, Neoplastic | Humans | Jurkat Cells | Lymphocyte Activation | Lymphocytes | Lymphoma | Lymphoproliferative Disorders | Mice | Mice, Inbred C57BL | Mice, Transgenic | MicroRNAs