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Gene Editing and Small Molecule Inhibitors of the RNA Binding Protein IGF2BP2/IMP2 Show its Potential as an

Shilpee Chanda1, Konstantin Lepikhov2, Charlotte Dahlem1

  • 1Department of Pharmacy, Pharmaceutical Biology, Saarland University, 66123 Saarbrücken, Germany.

Frontiers in Bioscience (Landmark Edition)
|January 30, 2024
PubMed
Abstract

Insights

Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is crucial for cancer cell growth and spread. Inhibiting IGF2BP2 in lung and liver cancer cells reduced proliferation, migration, and colony formation, suggesting it as a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), also known as IMP2, is an oncofetal protein frequently overexpressed in various cancers.
  • Previous studies demonstrated IGF2BP2's role in cancer hallmarks using colorectal cancer cells.

Purpose of the Study:

  • To functionally characterize the role of IGF2BP2 in lung and hepatocellular carcinoma cell lines.
  • To assess IGF2BP2 as a potential therapeutic target in these cancer types.

Main Methods:

  • CRISPR/Cas9 and prime editing were used to generate IGF2BP2 knockout cell lines.
  • Cell proliferation, colony formation, and migration were assessed in vitro.
  • Small-molecule inhibitors targeting IGF2BP2 were employed.

Main Results:

  • Biallelic IGF2BP2 knockout was challenging in some cell lines (A549, Huh7), with edited cells losing proliferative capacity.
  • Successful biallelic knockout in LLC1 cells and monoallelic knockouts in other lines showed reduced 2D proliferation and migration.
  • In 3D cultures, IGF2BP2 knockouts exhibited altered morphology and significantly reduced colony formation.
  • IGF2BP2 inhibitor compounds mimicked these effects, inhibiting colony formation.

Conclusions:

  • IGF2BP2 is essential for tumor cell proliferation, migration, and colony formation.
  • These findings validate IGF2BP2 as a potential therapeutic target for lung and hepatocellular carcinoma.
Keywords:
CRISPR/Cas9IGF2BP2/IMP2RNA binding proteincell migrationcell proliferationcolony formationhallmarks of cancerlive cell imaging

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