{Reference Type}: Journal Article
{Title}: Critical roles of the miR-17∼92 family in thymocyte development, leukemogenesis, and autoimmunity.
{Author}: Liao K;Chen P;Zhang M;Wang J;Hatzihristidis T;Lin X;Yang L;Yao N;Liu C;Hong Y;Li X;Liu H;Zúñiga-Pflücker JC;Love PE;Chen X;Liu WH;Zhao B;Xiao C;
{Journal}: Cell Rep
{Volume}: 43
{Issue}: 6
{Year}: 2024 Jun 25
暂无{DOI}: 10.1016/j.celrep.2024.114261
{Abstract}: 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.