2. Academic Validation
  3. PCBP2 mediates MTUS1 degradation through 3'-UTR binding to restrict pyroptosis and augment malignant progression in esophageal squamous cell carcinoma

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

  • Esophagus. 2026 Mar 19. doi: 10.1007/s10388-026-01188-1.
Chenming Jiang # 1,  Quanling Lu # 2,  An Wang 3,  Hao Chen 4,  Lishuai Yao 5
Affiliations

Affiliations

  • 1 Department General Surgery, Jingan District Centre Hospital of Shanghai Jingan, Branch Hugshan Hospital Affiliated to Fudan University, Shanghai, 200040, China.
  • 2 Department of Nursing, Huashan Hospital, Fudan University, Shanghai, 200040, China.
  • 3 Department of Thoracic Surgery, Huashan Hospital, Fudan University, Shanghai, 200040, China.
  • 4 Department of Thoracic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No.600 Yishan Road, Shanghai, 200030, China. [email protected].
  • 5 Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510620, Guangdong, China. [email protected].
  • # Contributed equally.
PMID: 41851529 DOI: 10.1007/s10388-026-01188-1
Abstract

Backgrounds: Esophageal squamous cell carcinoma (ESCC) exhibits aggressive malignant behaviors. Microtubule associated scaffold protein 1 (MTUS1) has been recognized as a potential tumor suppressor, yet its roles and functional mechanisms in ESCC remain unclear.

Material and methods: MTUS1 expression in ESCC was analyzed bioinformatically and validated in cell lines. MTUS1 overexpression or poly(rC) binding protein 2 (PCBP2) knockdown was achieved in KYSE450 and TE-1 cells via lentiviral vectors, followed by CCK-8, EdU, colony formation, and Transwell assays to analyze malignant properties. Pyroptosis was evaluated by live/dead staining, LDH/IL-1β release, MitoSOX Red staining, and transmission electron microscopy observation. Interactions between MTUS1 and PCBP2, a putative RNA-binding protein for MTUS1, were analyzed via RIP-qPCR and dual-luciferase reporter assays. In vivo chemotherapeutic response to 5-fluorouracil (5-FU) was tested in subcutaneous allograft models. Clinical relevance was examined using tissue microarrays (TMA).

Results: MTUS1 was downregulated in ESCC. Its overexpression suppressed cell expansion while inducing Pyroptosis, characterized by elevated ROS, LDH, IL-1β, cleaved-caspase-9, and GSDME-N. PCBP2 bound MTUS1's 3'-untranslated region (3'-UTR), promoting mRNA decay. PCBP2 knockdown increased MTUS1 expression, enhanced Pyroptosis, and inhibited malignant behaviors, effects attenuated by MTUS1 knockdown. In vivo, PCBP2 knockdown enhanced 5-FU chemotherapeutic efficacy via Pyroptosis, effects reversed by MTUS1 knockdown. TMA showed low MTUS1/high PCBP2 expression correlated with poor differentiation and advanced stage.

Conclusions: PCBP2 suppresses MTUS1 expression via 3'UTR-mediated degradation, inhibiting Pyroptosis and promoting ESCC progression, suggesting the PCBP2/MTUS1 axis as a potential therapeutic target to enhance chemotherapy efficacy.

Keywords

Chemoresistance; ESCC; MTUS1; PCBP2; Pyroptosis.

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  • HY-12466
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