RNA-binding protein insulin-like growth factor mRNA-binding protein 3 (IMP-3) promotes cell survival via insulin-like

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A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3
11:44

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3

Published on: January 24, 2016

Baisong Liao1, Yan Hu, Gary Brewer

  • 1Department of Molecular Genetics, Microbiology, and Immunology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.

The Journal of Biological Chemistry
|July 16, 2011
PubMed

Insights

The RNA-binding protein IMP-3 promotes cancer cell survival by enhancing insulin-like growth factor II (IGF-II) translation. Reducing IMP-3 increases sensitivity to ionizing radiation (IR)-induced apoptosis, suggesting IMP-3 as a potential therapeutic target.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Ionizing radiation (IR) triggers proapoptotic gene expression, inhibiting cell survival.
  • RNA-binding proteins regulate mRNA stability and translation, influencing cellular responses to stress.
  • The oncofetal protein IMP-3 is overexpressed in malignancies and linked to tumor aggressiveness.

Purpose of the Study:

  • To investigate the role of IMP-3 in ionizing radiation (IR)-induced apoptosis.
  • To determine if IMP-3 influences cell survival pathways in response to IR.
  • To explore IMP-3 as a potential therapeutic target for enhancing cancer treatment sensitivity.

Main Methods:

  • Utilized K562 chronic myeloid leukemia cells as a model for IR-induced apoptosis.
  • Employed small interfering RNA (siRNA) to knockdown IMP-3 expression.
  • Conducted gene reporter assays to analyze IMP-3's effect on IGF-II mRNA translation.
  • Assessed the impact of recombinant insulin-like growth factor II (IGF-II) on IR-induced apoptosis in IMP-3 knockdown cells.

Main Results:

  • Knockdown of IMP-3 significantly increased K562 cell susceptibility to IR-induced apoptosis.
  • IMP-3 knockdown led to reduced insulin-like growth factor II (IGF-II) production.
  • IMP-3 was found to promote IGF-II mRNA translation via its 5' untranslated region (UTR) during apoptosis.
  • Recombinant IGF-II partially rescued the apoptotic phenotype observed after IMP-3 knockdown.

Conclusions:

  • IMP-3 promotes cancer cell survival in response to ionizing radiation (IR) partly through the insulin-like growth factor II (IGF-II) pathway.
  • IMP-3 enhances IGF-II mRNA translation, contributing to cell survival under IR stress.
  • Targeting IMP-3 could potentially sensitize chronic myeloid leukemia (CML) cells and other cancers to IR therapy.

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