GSTP1敲低胰腺癌细胞的多组学分析揭示了氧化还原和代谢稳态的关键调节因子。

IF 1.7 4区 生物学 Q3 BIOLOGY
Biology Open Pub Date : 2025-08-15 Epub Date: 2025-08-14 DOI:10.1242/bio.061986
Jenna N Duttenhefner, Rahul R Singh, Katherine Schmidt, Katie M Reindl
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引用次数: 0

摘要

谷胱甘肽S转移酶pi-1 (GSTP1)是氧化稳态所必需的解毒酶。在癌症中,GSTP1与致瘤性、细胞周期进展和化疗耐药有关。虽然在各种模型中,GSTP1的缺失与癌症生长的减少有关,但其机制仍然知之甚少。本研究通过诱导敲低模型研究了GSTP1作为胰腺导管腺癌(PDAC)的治疗靶点。我们证明GSTP1的缺失会破坏氧化还原平衡,损害细胞存活,并诱导代谢适应。多组学分析表征了诱导GSTP1敲低对PDAC细胞转录组和蛋白质组的全球影响,鉴定了550个差异表达基因和62个蛋白。值得注意的是,其中43个在mRNA和蛋白质水平上表现出一致的调节。我们发现了关键应激反应蛋白的失调,包括参与一氧化氮代谢的二甲基精氨酸二甲氨基水解酶1 (DDAH1)和维持蛋白质稳态的蛋白质二硫异构酶A6 (PDIA6)。GSTP1、DDAH1和PDIA6之间的相互作用凸显了胰腺癌氧化还原调控的复杂性,并提示靶向GSTP1可能为PDAC提供一种新的治疗方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Multiomics analysis of GSTP1 knockdown pancreatic cancer cells reveals key regulators of redox and metabolic homeostasis.

Multiomics analysis of GSTP1 knockdown pancreatic cancer cells reveals key regulators of redox and metabolic homeostasis.

Multiomics analysis of GSTP1 knockdown pancreatic cancer cells reveals key regulators of redox and metabolic homeostasis.

Multiomics analysis of GSTP1 knockdown pancreatic cancer cells reveals key regulators of redox and metabolic homeostasis.

Glutathione S transferase pi-1 (GSTP1) is a detoxification enzyme essential for oxidative homeostasis. In cancer, GSTP1 has been implicated in tumorigenicity, cell cycle progression, and chemoresistance. While GSTP1 depletion has been associated with decreased cancer growth in various models, the mechanism remains poorly understood. This study investigates GSTP1 as a therapeutic target for pancreatic ductal adenocarcinoma (PDAC) using inducible knockdown models. We demonstrate that GSTP1 loss disrupts redox balance, impairs cell survival, and induces metabolic adaptations. Multiomics analysis characterized the global impact of inducible GSTP1 knockdown on the transcriptome and proteome of PDAC cells, identifying 550 differentially expressed genes and 62 proteins. Notably, 43 of these showed consistent regulation at both the mRNA and protein levels. We identify dysregulation of key stress response proteins, including dimethylarginine dimethylaminohydrolase 1 (DDAH1), involved in nitric oxide metabolism, and protein disulfide isomerase A6 (PDIA6), which maintains protein homeostasis. The interplay between GSTP1, DDAH1 and PDIA6 highlights the complexity of redox regulation in pancreatic cancer and suggests that targeting GSTP1 may offer a new therapeutic approach for PDAC.

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来源期刊
Biology Open
Biology Open BIOLOGY-
CiteScore
3.90
自引率
0.00%
发文量
162
审稿时长
8 weeks
期刊介绍: Biology Open (BiO) is an online Open Access journal that publishes peer-reviewed original research across all aspects of the biological sciences. BiO aims to provide rapid publication for scientifically sound observations and valid conclusions, without a requirement for perceived impact.
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