Lipid-Lowering Drug, Fenofibrate Combined with si-HOTAIR Can Effectively Inhibit the Proliferation of Gliomas

Abstract

Background: Fenofibrate is a fibric acid derivative known to have a lipid-lowering effect. Although fenofibrate-induced peroxisome proliferator-activated receptor alpha (PPARα) transcription activation has been shown to play an important role in the malignant progression of gliomas, the underlying mechanisms are poorly understood.Methods: In this study, we analyzed the TCGA database and found that there is a significant negative correlation between long non-coding RNA (lncRNA) HOTAIR and PPARα. Then we explored the molecular mechanism of lncRNA HOTAIR regulating PPARα from the level of in vitro cell lines and the level of nude mouse glioma model in vivo, and explored the effect of combined application of HOTAIR knocking down and fenofibrate treatment on glioma invasion.Results: For the first time, it was shown that after knocking down the expression of HOTAIR in gliomas, the expression of PPARα was significantly up-regulated, and the invasion and proliferation ability of gliomas were obviously inhibited. Then, glioma cells were treated with both PPARα agonist, fenofibrate and si-HOTAIR; results showed that proliferation and invasion of glioma cells were significantly inhibited.Conclusions: Our results suggest that HOTAIR can negatively regulate the expression of PPARα, and the combination of fenofibrate and si-HOTAIR treatment can significantly inhibit the progression of gliomas. This introduces new ideas for the treatment of gliomas.