Notch-mediated repression of miR-223 contributes to IGF1R regulation in T-ALL

Leuk Res. 2012 Jul;36(7):905-11. doi: 10.1016/j.leukres.2012.02.013. Epub 2012 Mar 17.

Abstract

To identify microRNAs regulated by oncogenic Notch signaling, we performed microarray-based miRNA profiling of T-cell acute lymphoblastic leukemia (T-ALL) cells before and after treatment with γ-secretase inhibitor (GSI) to block Notch signaling. We show miR-223 levels increase after GSI treatment suggesting that active Notch signaling represses miR-223 expression. We also demonstrate that insulin-like growth factor-1 receptor (IGF1R) is regulated by miR-223 in this context, but observe no apparent effects on cell growth by overexpression or knock-down of miR-223 alone. We conclude that miR-223 contributes to IGF1R regulation, but may act in concert with other genes and/or microRNAs to alter T-ALL biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation
  • Down-Regulation / genetics
  • Down-Regulation / physiology
  • Gene Expression Profiling
  • Gene Expression Regulation, Leukemic
  • HEK293 Cells
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / physiology
  • Microarray Analysis
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Receptor, IGF Type 1 / genetics*
  • Receptor, IGF Type 1 / metabolism
  • Receptor, Notch1 / genetics
  • Receptor, Notch1 / metabolism
  • Receptor, Notch1 / physiology*
  • Transfection
  • Validation Studies as Topic

Substances

  • MIRN223 microRNA, human
  • MicroRNAs
  • NOTCH1 protein, human
  • Receptor, Notch1
  • Receptor, IGF Type 1