胸腺细胞发育需要精确控制 PI3K-Akt 信号传导，以促进增殖并预防白血病和自身免疫性疾病。在这里，我们表明，消除 miR-17∼92 家族的单个簇对胸腺细胞发育的影响可以忽略不计，而删除整个家族会严重损害胸腺细胞增殖并减少胸腺细胞结构，表型复制 Dicer 基因删除。从机制上讲，miR-17∼92的表达是由Myc介导的前T细胞受体（TCR）信号传导诱导的，并且miR-17∼92通过抑制Pten的翻译来促进胸腺细胞增殖。 miR-17∼92的逆转录病毒表达可恢复Myc缺陷型胸腺细胞的增殖和分化。相反，部分删除 miR-17∼92 家族可显着延迟 Myc 驱动的白血病发生。有趣的是，胸腺细胞特异性转基因miR-17∼92表达不会引起白血病或淋巴瘤，而是会加重皮肤炎症，而消除miR-17∼92家族会改善皮肤炎症。这项研究揭示了 miR-17∼92 家族在平衡胸腺细胞发育、白血病发生和自身免疫方面的复杂作用，并将这些 microRNA (miRNA) 确定为白血病和自身免疫性疾病的潜在治疗靶点。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。

Thymocyte development requires precise control of PI3K-Akt signaling to promote proliferation and prevent leukemia and autoimmune disorders. Here, we show that ablating individual clusters of the miR-17∼92 family has a negligible effect on thymocyte development, while deleting the entire family severely impairs thymocyte proliferation and reduces thymic cellularity, phenocopying genetic deletion of Dicer. Mechanistically, miR-17∼92 expression is induced by Myc-mediated pre-T cell receptor (TCR) signaling, and miR-17∼92 promotes thymocyte proliferation by suppressing the translation of Pten. Retroviral expression of miR-17∼92 restores the proliferation and differentiation of Myc-deficient thymocytes. Conversely, partial deletion of the miR-17∼92 family significantly delays Myc-driven leukemogenesis. Intriguingly, thymocyte-specific transgenic miR-17∼92 expression does not cause leukemia or lymphoma but instead aggravates skin inflammation, while ablation of the miR-17∼92 family ameliorates skin inflammation. This study reveals intricate roles of the miR-17∼92 family in balancing thymocyte development, leukemogenesis, and autoimmunity and identifies those microRNAs (miRNAs) as potential therapeutic targets for leukemia and autoimmune diseases.Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.