Targeting PTBP3-Mediated Alternative Splicing of COX11 Induces Cuproptosis for Inhibiting Gastric Cancer Peritoneal Metastasis.

ABSTRACT: Numerous aberrant splicing events are implicated in tumor progression, yet comprehensive reports on splicing factors and events associated with peritoneal metastasis in gastric cancer (GCPM) are lacking. In this study, PTBP3 is found to be significantly overexpressed in peritoneal metastatic tissues of gastric cancer compared to primary tumor tissues, and higher PTBP3 expression correlates with poorer prognosis. Using gastric cancer cells and patient-derived organoids (PDO), the role of PTBP3 in promoting tumor invasion and proliferation is investigated. Mechanistically, through full-length transcriptome sequencing, PTBP3 mediates exon 4 skipping in its target gene COX11, leading to shorter transcripts that impair COX11 protein function, reducing mitochondrial copper content and enabling t

SUBMITTER: Zhou Y 

PROVIDER: S-EPMC12140345 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature