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RNA Binding Protein PTBP1 Promotes the Metastasis of Gastric Cancer by Stabilizing PGK1 mRNA.

Cells | 2024

Gastric cancer (GC) is the most common type of malignant tumor within the gastrointestinal tract, and GC metastasis is associated with poor prognosis. Polypyrimidine tract binding protein 1 (PTBP1) is an RNA-binding protein implicated in various types of tumor development and metastasis. However, the role of PTBP1 in GC metastasis remains elusive. In this study, we verified that PTBP1 was upregulated in GC tissues and cell lines, and higher PTBP1 level was associated with poorer prognosis. It was shown that PTBP1 knockdown in vitro inhibited GC cell migration, whereas PTBP1 overexpression promoted the migration of GC cells. In vivo, the knockdown of PTBP1 notably reduced both the size and occurrence of metastatic nodules in a nude mice liver metastasis model. We identified phosphoglycerate kinase 1 (PGK1) as a downstream target of PTBP1 and found that PTBP1 increased the stability of PGK1 by directly binding to its mRNA. Furthermore, the PGK1/SNAIL axis could be required for PTBP1's function in the promotion of GC cell migration. These discoveries suggest that PTBP1 could be a promising therapeutic target for GC.

Pubmed ID: 38247832 RIS Download

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Associated grants

  • Agency: National Natural Science Foundation of China,
    Id: 82073254
  • Agency: National Natural Science Foundation of China,
    Id: 81872392
  • Agency: Chongqing Talents-Exceptional Young Talents Project,
    Id: CQYC202005044
  • Agency: Chongqing Talents-Exceptional Young Talents Project,
    Id: CSTC2021YCJH-BGZXM0094
  • Agency: Chongqing Natural Science Foundation Innovation and Development Joint Fund,
    Id: CSTB2022NSCQ-LZX0043
  • Agency: Science and Technology Research Project of Chongqing Municipal Education Commission,
    Id: KJZD-K202100405
  • Agency: Future Medical Youth Innovation Team Project of Chongqing Medical University,
    Id: W0042
  • Agency: Graduate Tutor Team Construction Project of Chongqing,
    Id: CQMUDSTD202210
  • Agency: Chongqing Graduate Scientific Research Innovation Project,
    Id: CYB22221

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