Bioinformatics-based discovery of the involvement of PSAT1 in mediating the anti-lung adenocarcinoma activity of triptolide

Abstract

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.

Keywords

bioinformatics / gemcitabine resistance / lung adenocarcinoma / PSAT1 / triptolide

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2026 The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.