| First Author | Liao K | Year | 2024 |
| Journal | Cell Rep | Volume | 43 |
| Issue | 6 | Pages | 114261 |
| PubMed ID | 38776224 | Mgi Jnum | J:351313 |
| Mgi Id | MGI:7665966 | Doi | 10.1016/j.celrep.2024.114261 |
| Citation | Liao K, et al. (2024) Critical roles of the miR-17 approximately 92 family in thymocyte development, leukemogenesis, and autoimmunity. Cell Rep 43(6):114261 |
| abstractText | 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 approximately 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 approximately 92 expression is induced by Myc-mediated pre-T cell receptor (TCR) signaling, and miR-17 approximately 92 promotes thymocyte proliferation by suppressing the translation of Pten. Retroviral expression of miR-17 approximately 92 restores the proliferation and differentiation of Myc-deficient thymocytes. Conversely, partial deletion of the miR-17 approximately 92 family significantly delays Myc-driven leukemogenesis. Intriguingly, thymocyte-specific transgenic miR-17 approximately 92 expression does not cause leukemia or lymphoma but instead aggravates skin inflammation, while ablation of the miR-17 approximately 92 family ameliorates skin inflammation. This study reveals intricate roles of the miR-17 approximately 92 family in balancing thymocyte development, leukemogenesis, and autoimmunity and identifies those microRNAs (miRNAs) as potential therapeutic targets for leukemia and autoimmune diseases. |
