MicroRNA let-7i induced autophagy to protect T cell from apoptosis by targeting IGF1R

Biochem Biophys Res Commun. 2014 Oct 31;453(4):728-34. doi: 10.1016/j.bbrc.2014.10.002. Epub 2014 Oct 8.

Abstract

MicroRNA let-7i is up-regulated in T cells from patients with Ankylosing Spondylitis (AS). In this study, we investigated the role of let-7i in T cells survival. Our results demonstrated down-regulation of insulin-like growth factor-1 receptor (IGF1R) in T cells from patients with AS. Luciferase reporter assay suggested IGF1R as direct target of let-7i. Overexpression of let-7i in Jurkat cells significantly suppressed IGF1R expression, which mimicked the action of IGF1R siRNA. IGF1R inhibition led to a strinking decrease in phosphorylation of mTOR and Akt, down-regulation of Bcl-2, up-regulation of Bax and cleavage of caspase 3 and PARP. Meanwhile, IGF1R inhibition induced autophagy. Autophagy induced by let-7i overexpression contributed to protect cells from apoptosis. Our data indicated that let-7i might control T cells fates in AS by targeting IGF1R.

Keywords: Ankylosing Spondylitis; Apoptosis; Autophagy; IGF1R; MicroRNA let-7i.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / genetics*
  • Autophagy
  • Cells, Cultured
  • Gene Silencing
  • Gene Targeting / methods*
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / pharmacology
  • Receptor, IGF Type 1 / genetics*
  • Spondylitis, Ankylosing / genetics*
  • Spondylitis, Ankylosing / pathology*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / pathology*

Substances

  • MIRNLET7 microRNA, rat
  • MicroRNAs
  • Receptor, IGF Type 1