ArticleEsophagus : official journal of the Japan Esophageal Society2026
PCBP2 mediates MTUS1 degradation through 3'-UTR binding to restrict pyroptosis and augment malignant progression in esophageal squamous cell carcinoma.
Article in Esophagus : official journal of the Japan Esophageal Society, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundsEsophageal 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
methodsMTUS1 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).
resultsMTUS1 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.
conclusionsPCBP2 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.
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