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

IF 6.1 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Apoptosis Pub Date : 2024-12-25 DOI:10.1007/s10495-024-02049-x
Mingrui Jiang, Sen Wang, Jin Ji, Shantanu Baral, Qiannan Sun, Yong Wang, Bin Liu, Jun Ren, Wei Wang, Daorong Wang
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Abstract

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.

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PWP1通过转录调控p53,调节细胞凋亡和细胞周期,促进胃癌进展。
胃癌仍然是世界范围内癌症相关死亡的主要原因。预后往往取决于早期发现和了解其进展的分子机制。周期性色氨酸蛋白1 (PWP1)已成为一种新的诊断标志物,可能与胃癌进展有关。本研究旨在阐明PWP1对胃癌发生发展的影响,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研究Pwp1的表达及其功能作用。采用定量PCR和Western blot检测PWP1的表达水平。通过流式细胞术和TUNEL检测细胞凋亡,通过细胞周期分析评估PWP1调节对细胞凋亡的影响。动物实验采用小鼠模型注射PWP1敲低或过表达的胃癌细胞,观察肿瘤的生长和进展。采用t检验和方差分析评估统计显著性。与正常组织相比,胃癌组织中PWP1表达升高。PWP1的敲低导致细胞凋亡增加,细胞周期阻滞在G1期,提示其在促进侵袭和增殖中的作用。此外,动物实验表明,敲低PWP1小鼠的肿瘤生长减少。发现PWP1通过转录调控p53,影响其表达,从而影响胃癌细胞凋亡和细胞周期通路。我们的研究发现PWP1是胃癌(GC)中经常过表达的一种新型癌基因。PWP1通过转录调控p53,影响细胞凋亡,诱导G1期细胞周期阻滞,从而促进细胞生长。这些发现强调PWP1是治疗GC的一个有希望的治疗靶点,表明其未来的临床应用潜力。
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来源期刊
Apoptosis
Apoptosis 生物-生化与分子生物学
CiteScore
9.10
自引率
4.20%
发文量
85
审稿时长
1 months
期刊介绍: Apoptosis, a monthly international peer-reviewed journal, focuses on the rapid publication of innovative investigations into programmed cell death. The journal aims to stimulate research on the mechanisms and role of apoptosis in various human diseases, such as cancer, autoimmune disease, viral infection, AIDS, cardiovascular disease, neurodegenerative disorders, osteoporosis, and aging. The Editor-In-Chief acknowledges the importance of advancing clinical therapies for apoptosis-related diseases. Apoptosis considers Original Articles, Reviews, Short Communications, Letters to the Editor, and Book Reviews for publication.
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