DOI: 10.1002/ame2.70120
Bioinformatics-based discovery of the involvement of PSAT1 in mediating the anti-lung adenocarcinoma activity of triptolide
Zhiwen Cao1
Lulu Zhang2
Wenqiang Zhang3
Rong Wan3
Xiaogang Peng3
Jinyan Xie3
Ruru Bai3
Jiejing Jin3
Changqi Shi2
Lan Yan2
Xiangyu Guo4
Yang Shen1
Cheng Lu2
1.Jiangxi Provincial Key Laboratory of Molecular Medicine,The Second Affiliated Hospital of Nanchang University,Jiangxi Medical College,Nanchang University,Nanchang,China;Department of Genetic Medicine,The Second Affiliated Hospital of Nanchang University,Jiangxi Medical College,Nanchang University,Nanchang,China2.Institute of Basic Research in Clinical Medicine,China Academy of Chinese Medical Sciences,Beijing,China3.Jiangxi Provincial Key Laboratory of Molecular Medicine,The Second Affiliated Hospital of Nanchang University,Jiangxi Medical College,Nanchang University,Nanchang,China4.Department of Endocrinology,Dongfang Hospital of Beijing University of Chinese Medicine,Beijing,China
摘要：Background:Triptolide(TP)exhibits various pharmacological activities.Our previous studies have confirmed the efficacy of TP against lung adenocarcinoma(LUAD).However,the potent pharmacological activity of TP is underpinned by its complex mechanisms.Exploring its potential mechanisms is of great value for promoting the clinical application of TP and extending its clinical use.
Methods:Differentially expressed genes(DEGs)associated with LUAD were analyzed and acquired from the TCGA database,while DEGs related to TP were obtained through RNA sequencing.Hub genes were identified through LASSO and random forest models.The efficacy of TP against LUAD was validated using tumor-bearing mouse models and A549 cells.The validation of hub genes was conducted using RT-qPCR.The regulatory effect of hub genes on TP efficacy was validated through overexpression cell models.Furthermore,the potential mechanisms by which TP improves gemcitabine(GEM)resistance were explored using a GEM-resistant cell line in combination with the overexpression model.
Results:This study validated the therapeutic effect of TP against LUAD in vivo and in vitro.Bioinformatics revealed that the mechanism of TP's effect against LUAD might be associated with amino acid-related biological processes.Five hub genes were screened and identified by combining bioinformatics methods and experiments.The overexpression model validated that PSAT1 plays an effective role in the efficacy of TP and in alleviating GEM resistance.
Conclusion:This study preliminarily demonstrated that the anti-LUAD effect of TP was associated with the PSAT1-regulated serine biosynthesis pathway,and that TP effectively improves GEM resistance by inhibiting PSAT1 expression.
机标关键词：involvementbioinformaticsdiscoveryactivityadenocarcinomaanti-lungbasedmediating
论文发表日期：2026-01-30
在线出版日期：2026-03-27（本平台首次上网日期，不代表文献的发表时间）
页数：13( 115-127 )
英文信息