IGF2BP3-mediated regulation of the RNA isoform and modification landscape in pancreatic cancer

Sandra Margielewska-Davies1, Wayne Croft1, Hayden Pearce1

  • 1School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham, UK.

Oncogene
|August 7, 2026
PubMed

Insights

Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) is crucial for pancreatic ductal adenocarcinoma (PDAC) progression. Targeting IGF2BP3 may offer a new therapeutic strategy for this aggressive cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • RNA Biology

Background:

  • Pancreatic ductal adenocarcinoma (PDAC) incidence is rising with poor clinical outcomes.
  • IGF2BP3, an oncofetal RNA regulatory protein, is highly expressed in PDAC and a potential therapeutic target.

Purpose of the Study:

  • To investigate the role of IGF2BP3 in PDAC progression and its potential as a therapeutic target.

Main Methods:

  • siRNA knockdown of IGF2BP3 in PDAC cells and organoids.
  • Direct RNA sequencing to analyze IGF2BP3-mediated RNA splicing and modification.
  • Analysis of RNA modifications (m6A, m5C, pseudouridine) in PDAC transcriptome.

Main Results:

  • IGF2BP3 knockdown suppressed PDAC cell proliferation, DNA replication, cell cycle, TNF signaling, and epithelial-mesenchymal transition.
  • IGF2BP3 significantly altered RNA splicing and modification patterns, impacting miRNA and scRNA.
  • IGF2BP3 is essential for malignant stem cell proliferation and survival in PDAC organoids.

Conclusions:

  • IGF2BP3 consistently expressed in PDAC, plays a dominant role in RNA regulation.
  • IGF2BP3 supports PDAC stem cell survival and proliferation, making it a critical therapeutic target.

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