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Detection of Alternative Splicing During Epithelial-Mesenchymal Transition
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PTBP2-Mediated Alternative Splicing of IRF9 Controls Tumor-Associated Monocyte/Macrophage Chemotaxis and

Jue Tang1, Jing He1, Huiqin Guo1,2

  • 1Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China.

Research (Washington, D.C.)
|April 11, 2023
PubMed

Insights

Polypyrimidine tract binding protein 2 (PTBP2) in neuroblastoma (NB) cells attracts monocytes and macrophages, inhibiting tumor growth. This PTBP2-induced immune response predicts a favorable prognosis in mediastinal NB.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Mediastinal neuroblastoma (NB) recurrence and metastasis remain significant challenges post-treatment.
  • Tumor microenvironment modulation shows promise, yet the roles of monocytes and macrophages in NB are underexplored.

Purpose of the Study:

  • To investigate the role of polypyrimidine tract binding protein 2 (PTBP2) in mediastinal NB.
  • To elucidate the mechanisms by which PTBP2 influences the tumor microenvironment, specifically monocytes and macrophages.

Main Methods:

  • Proteomic profiling to identify potential biomarkers in mediastinal NB.
  • Functional studies assessing the impact of PTBP2 on monocyte/macrophage activity and NB progression.
  • Mechanistic investigations involving RNA splicing, interferon signaling, and chemokine secretion.

Main Results:

  • PTBP2 was identified as a potential biomarker in mediastinal NB, correlating with good outcomes.
  • PTBP2 expression in NB cells promoted monocyte and macrophage chemotaxis and repolarization, inhibiting tumor growth and metastasis.
  • PTBP2 was found to regulate interferon regulatory factor 9 splicing and enhance type I interferon secretion via STAT1 and CCL5, driving monocyte/macrophage recruitment and maintaining a proinflammatory phenotype.

Conclusions:

  • PTBP2 plays a critical role in modulating the immune microenvironment in NB by influencing monocyte and macrophage functions.
  • PTBP2-mediated RNA splicing enhances immune compartmentalization between NB cells and monocytes, contributing to a favorable prognosis.
  • PTBP2 represents a potential therapeutic target and prognostic marker for mediastinal neuroblastoma.

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