Triptolide Treatment for Oral Squamous Cell Carcinoma by Regulating the LncRNA‐MSTRG.24214.1/MiRNA‐939‐5p/LCN2 Axis

ABSTRACT Background Although triptolide has demonstrated efficacy in treating oral squamous cell carcinoma (OSCC), its precise molecular mechanism remains unclear. This study investigated the mechanism underlying triptolide's action in lncRNA‐mediated competing endogenous RNA (ceRNA) regulation. Methods The impact of triptolide on OSCC in vivo was validated using a xenograft tumor model. Whole‐transcriptome sequencing and bioinformatics analysis were conducted to construct the lncRNA‐miRNA‐mRNA regulatory network. Relative gene and protein expression levels were confirmed using qRT‐PCR and Western blot. Dual‐luciferase assays were performed to assess target interactions, while cell proliferation was measured using CCK8 assays, and cell migration and invasion were evaluated via wound healing and transwell assays. Results Triptolide markedly reduced proliferation, migration, and invasion in Cal27 and Tca8113 cells. After 22 days of triptolide treatment, the tumor volume of mice gradually shrank. This led to significant upregulation of cleaved Caspase‐3 and Bax, alongside downregulation of Bcl‐2. Transcriptome sequencing and bioinformatics analysis identified 266 differentially expressed mRNAs, 528 lncRNAs, and 85 miRNAs. Enhanced expression of lncRNA MSTRG.24214.1 and mRNA LCN2, along with reduced expression of miR‐939‐5p, was observed in the triptolide group. Conclusions The lncRNA‐miRNA‐mRNA ceRNA network associated with triptolide's impact on OSCC was successfully established. Triptolide suppressed OSCC development and progression both in vitro and in vivo, potentially through modulation of the MSTRG.24214.1‐miR‐939‐5p‐LCN2 axis. These findings offer a solid foundation for future personalized triptolide‐based therapeutic approaches.