Conclusion
This study reveals that TRIB3 promotes OSCC growth by regulating JNK/JUN pathway-mediated aerobic glycolysis, and TRIB3 may be a potential target for treating OSCC.
Methods
We analyzed the expression of TRIB3 in the TCGA database for clinical tissue samples, in vitro, and in vivo. Cell proliferation, migration, invasion, and apoptosis were observed by overexpressing or knocking down TRIB3. Crucially, the impact of TRIB3 on aerobic glycolysis in OSCC was also probed in our study, including glucose uptake, lactate content, ATP production, extracellular acidification rate, and oxygen consumption rate. Importantly, we examined the relationship between TRIB3 and the JNK/JUN pathway and whether it regulates glycolytic processes in OSCC cells through the JNK/JUN pathway. Finally, tumor growth in vivo was tested using Xenograft models to observe the effect of knockdown TRIB3.
Objective
The potentiation of glycolysis is a leading driver of squamous cell carcinoma. Targeted modulation of the glycolytic process might be a pivotal tool for treating squamous cell carcinoma. Tribble homolog 3 (TRIB3) expression is elevated in some squamous cell carcinomas and correlates with poor prognosis. We investigated whether increased TRIB3 expression contributes to the progression of oral squamous cell carcinoma (OSCC) by modulating glycolysis.
Results
Our study identified TRIB3 as the most variable and prognostic in OSCC. A significant high expression of TRIB3 in OSCC cells was determined in vitro and promoted cell proliferation, migration, invasion, apoptosis, and aerobic glycolysis. Knockdown of TRIB3 produced opposite effects. In addition, these effects are regulated by the JNK/JUN pathway. The use of JNK inhibitor inhibited the pro-growth and glycolytic effects of TRIB3 on OSCC cells. Finally, we further determined that TRIB3 knockdown would effectively suppress tumor growth in vivo.