Critical roles of the miR-17∼92 family in thymocyte development, leukemogenesis, and autoimmunity. Academic Article uri icon

Overview

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.

authors

  • Liao, Kunyu
  • Chen, Pengda
  • Zhang, Mengdi
  • Wang, Jiazhen
  • Hatzihristidis, Teri
  • Lin, Xiaoxi
  • Yang, Liang
  • Yao, Nan
  • Liu, Chenfeng
  • Hong, Yazhen
  • Li, Xia
  • Liu, Hong
  • Zúñiga-Pflücker, Juan Carlos
  • Love, Paul E
  • Chen, Xiang
  • Liu, Wen-Hsien
  • Zhao, Bin
  • Xiao, Changchun

publication date

  • May 22, 2024

Research

keywords

  • Autoimmunity
  • Leukemia
  • MicroRNAs
  • Thymocytes

Identity

Scopus Document Identifier

  • 85193507142

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2024.114261

PubMed ID

  • 38776224

Additional Document Info

volume

  • 43

issue

  • 6