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PCBP2 mediates MTUS1 degradation through 3'-UTR binding to restrict pyroptosis and augment malignant progression in

Chenming Jiang1, Quanling Lu2, An Wang3

  • 1Department General Surgery, Jingan District Centre Hospital of Shanghai Jingan, Branch Hugshan Hospital Affiliated to Fudan University, Shanghai, 200040, China.

Esophagus : Official Journal of the Japan Esophageal Society
|March 19, 2026
PubMed
Abstract

Insights

Poly(rC) binding protein 2 (PCBP2) suppresses Microtubule associated scaffold protein 1 (MTUS1) in esophageal cancer. Targeting the PCBP2/MTUS1 axis may enhance chemotherapy efficacy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Esophageal squamous cell carcinoma (ESCC) is aggressive.
  • Microtubule associated scaffold protein 1 (MTUS1) is a potential tumor suppressor.
  • MTUS1's role in ESCC is unclear.

Purpose of the Study:

  • Investigate MTUS1's function in ESCC.
  • Elucidate the regulatory mechanism of MTUS1.
  • Explore the therapeutic potential of the MTUS1 pathway.

Main Methods:

  • Bioinformatic analysis and cell line validation of MTUS1 expression.
  • In vitro assays (CCK-8, EdU, colony formation, Transwell) to assess malignant properties.
  • Pyroptosis evaluation (live/dead staining, LDH/IL-1β release, MitoSOX, TEM).
  • RNA-binding assays (RIP-qPCR, dual-luciferase) to confirm MTUS1-PCBP2 interaction.
  • In vivo chemotherapeutic response studies (5-FU) and clinical correlation (TMA).

Main Results:

  • MTUS1 was downregulated in ESCC.
  • MTUS1 overexpression suppressed proliferation and induced pyroptosis.
  • PCBP2 binds MTUS1 3'-UTR, promoting mRNA decay.
  • PCBP2 knockdown increased MTUS1, enhanced pyroptosis, and inhibited ESCC progression.
  • PCBP2 knockdown improved 5-FU efficacy in vivo via pyroptosis.
  • Low MTUS1/high PCBP2 expression correlated with poor prognosis.

Conclusions:

  • PCBP2 suppresses MTUS1 via 3'-UTR-mediated degradation, inhibiting pyroptosis and promoting ESCC.
  • The PCBP2/MTUS1 axis is a potential therapeutic target for enhancing chemotherapy efficacy in ESCC.
Keywords:
ChemoresistanceESCCMTUS1PCBP2Pyroptosis

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