PWP1 transcriptionally regulates p53, modulating apoptosis and cell cycle to promote gastric cancer progression

被引：1

作者：

Mingrui Jiang ^{[1
]}

Sen Wang ^{[2
]}

Jin Ji ^{[3
]}

Shantanu Baral ^{[1
]}

Qiannan Sun ^{[2
]}

Yong Wang ^{[1
]}

Bin Liu ^{[2
]}

Jun Ren ^{[4
]}

Wei Wang ^{[4
]}

Daorong Wang ^{[4
]}

机构：

[1] Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou

[2] Medical College of Yangzhou University, Yangzhou

[3] The First Affiliated Hospital With Nanjing Medical University, Nanjing

[4] Northern Jiangsu People’s Hospital, Yangzhou

[5] General Surgery Institute of Yangzhou, Yangzhou University, Yangzhou

来源：

Apoptosis | 2025年 / 30卷 / 3期

基金：

中国国家自然科学基金;

关键词：

Apoptosis; Cell cycle; Gastric cancer; p53; PWP1;

D O I：

10.1007/s10495-024-02049-x

中图分类号：

学科分类号：

摘要：

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. © The Author(s) 2024.

引用

页码：693 / 709

页数：16

共 33 条

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