College of Pharmacy, Chongqing Medical University, Chongqing 400016, China.
Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563006, China.
Cells. 2024 Jan 12;13(2):140. doi: 10.3390/cells13020140.
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 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.
胃癌(GC)是胃肠道中最常见的恶性肿瘤类型,GC 转移与预后不良相关。多嘧啶 tract 结合蛋白 1(PTBP1)是一种 RNA 结合蛋白,参与多种类型的肿瘤发生和转移。然而,PTBP1 在 GC 转移中的作用仍不清楚。在本研究中,我们验证了 PTBP1 在 GC 组织和细胞系中上调,并且较高的 PTBP1 水平与预后不良相关。结果表明,体外敲低 PTBP1 抑制了 GC 细胞迁移,而过表达 PTBP1 则促进了 GC 细胞的迁移。在体内,敲低 PTBP1 显著减少了裸鼠肝转移模型中转移结节的大小和发生。我们确定磷酸甘油酸激酶 1(PGK1)是 PTBP1 的下游靶标,并发现 PTBP1 通过直接结合其 mRNA 增加了的稳定性。此外,PGK1/SNAIL 轴可能是 PTBP1 促进 GC 细胞迁移功能所必需的。这些发现表明,PTBP1 可能是 GC 的一个有前途的治疗靶点。