%0 Journal Article
%T Critical roles of the miR-17∼92 family in thymocyte development, leukemogenesis, and autoimmunity.
%A Liao K
%A Chen P
%A Zhang M
%A Wang J
%A Hatzihristidis T
%A Lin X
%A Yang L
%A Yao N
%A Liu C
%A Hong Y
%A Li X
%A Liu H
%A Zúñiga-Pflücker JC
%A Love PE
%A Chen X
%A Liu WH
%A Zhao B
%A Xiao C
%J Cell Rep
%V 43
%N 6
%D 2024 Jun 25
%M 38776224
暂无%R 10.1016/j.celrep.2024.114261
%X 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.