Jiang Mingrui, Wang Sen, Ji Jin, Baral Shantanu, Sun Qiannan, Wang Yong, Liu Bin, Ren Jun, Wang Wei, Wang Daorong
Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, 225001, China.
Medical College of Yangzhou University, Yangzhou, 225001, China.
Apoptosis. 2025 Apr;30(3-4):693-709. doi: 10.1007/s10495-024-02049-x. Epub 2024 Dec 25.
Gastric cancer remains a leading cause of cancer-related mortality worldwide. The prognosis often depends on early detection and understanding the molecular mechanisms involved in its progression. Periodic tryptophan protein 1 (PWP1) has emerged as a novel diagnostic marker, potentially linked to gastric cancer progression. This study aims to elucidate the impact of PWP1 on gastric cancer development, focusing on apoptosis, cell cycle regulation, and the role of p53. This study utilized gastric cancer cell lines to investigate the expression and functional role of Pwp1. Quantitative PCR and Western blot analyses were conducted to measure PWP1 expression levels. Apoptosis was assessed by using flow cytometry and TUNEL assays, and cell cycle analysis was performed to evaluate the impact of PWP1 modulation. Additionally, animal experiments were conducted using mouse models injected with gastric cancer cells, with PWP1 knockdown or overexpression, to observe tumor growth and progression. Statistical significance was evaluated using t-tests and ANOVA where appropriate. Elevated PWP1 expression was observed in gastric cancer tissues compared to normal tissues. PWP1's knockdown resulted in increased apoptosis and cell cycle arrest at the G1 phase, suggesting its role in promoting invasion and proliferation. Furthermore, animal experiments demonstrated reduced tumor growth in mice with PWP1 knockdown. PWP1 was found to transcriptionally regulate p53, affecting its expression and thereby influencing apoptosis and cell cycle pathways in gastric cancer. Our study identifies PWP1 as a novel oncogene frequently overexpressed in gastric cancer (GC). Through transcriptional regulation of p53, PWP1 enhances cell growth by influencing apoptosis and inducing G1 phase cell cycle arrest. These findings underscore PWP1 as a promising therapeutic target for treating GC, suggesting its potential for future clinical applications.
胃癌仍然是全球癌症相关死亡的主要原因。其预后通常取决于早期检测以及对其进展过程中涉及的分子机制的了解。周期性色氨酸蛋白1(PWP1)已成为一种新型诊断标志物,可能与胃癌进展有关。本研究旨在阐明PWP1对胃癌发展的影响,重点关注细胞凋亡、细胞周期调控以及p53的作用。本研究利用胃癌细胞系来研究Pwp1的表达及其功能作用。采用定量PCR和蛋白质免疫印迹分析来检测PWP1的表达水平。通过流式细胞术和TUNEL检测评估细胞凋亡,并进行细胞周期分析以评估PWP1调节的影响。此外,使用注射了胃癌细胞的小鼠模型进行动物实验,通过敲低或过表达PWP1来观察肿瘤的生长和进展。在适当情况下,使用t检验和方差分析评估统计学意义。与正常组织相比,胃癌组织中观察到PWP1表达升高。敲低PWP1导致细胞凋亡增加和细胞周期在G1期停滞,表明其在促进侵袭和增殖中的作用。此外,动物实验表明敲低PWP1的小鼠肿瘤生长减缓。发现PWP1可转录调节p53,影响其表达,从而影响胃癌中的细胞凋亡和细胞周期途径。我们的研究确定PWP1是一种在胃癌(GC)中经常过度表达的新型癌基因。通过对p53的转录调节,PWP1通过影响细胞凋亡和诱导G1期细胞周期停滞来促进细胞生长。这些发现强调PWP1是治疗GC的一个有前景的治疗靶点,表明其在未来临床应用中的潜力。