Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes
Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes
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DOI：
10.1038/ni1575
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发表时间：
2008-04-01
影响因子：
30.5
通讯作者：
Rajewsky, Klaus
中科院分区：
文献类型：
--
作者：
Xiao, Changchun;Srinivasan, Lakshmi;Rajewsky, Klaus
编码miR-17-92microRNA(MiRNA)簇的基因组区域在淋巴瘤和其他癌症中经常被扩增，携带该扩增片段的癌细胞在该簇中有较高的miRNA表达。MiR-17-92的逆转录病毒表达加速了c-Myc诱导的淋巴瘤的发展，但确切地说，miR-17-92的高表达如何促进淋巴肿大仍不清楚。在这里，我们产生了淋巴细胞中miR-17-92表达较高的小鼠。这些小鼠患上淋巴增生性疾病和自身免疫，并过早死亡。这些小鼠的淋巴细胞表现出更多的增殖和更少的激活诱导的细胞死亡。MiR-17-92miRNA抑制肿瘤抑制基因PTEN和促凋亡蛋白Bim的表达。这种机制可能与miR-17-92转基因小鼠的淋巴增殖性疾病和自身免疫有关，也可能是miR-17-92编码区扩增患者发生淋巴瘤的原因之一。
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.