Wei Zhu1,2,3, Hongyang Zhao4, Fenfen Xu4, Bin Huang1,2, Xiaojing Dai5, Jikui Sun6,7,8, Alphonce M K Nyalali1,2,9, Kailiang Zhang10,11, Shilei Ni12,13. 1. Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, 250012, Shandong, China. 2. Key Laboratory of Brain Function Remodeling, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, China. 3. Department of Neurosurgery, Yantai Yuhuangding Hospital, Cheeloo College of Medicine, Shandong University, Yantai, 264000, Shandong, China. 4. Department of Pediatrics, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250013, Shandong, China. 5. The Advanced Technology Genomics Core, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. 6. School of Medicine, Nankai University, 94 Weijin Road, Tianjin, 300071, China. 7. Tianjin Cerebral Vascular and Neural Degenerative Disease Key Laboratory, Tianjin Neurosurgical Institute, Tianjin, 30350, China. 8. Department of Neurosurgery, Tianjin Huanhu Hospital, Tianjin, 300350, China. 9. Department of Orthopedics and Neurosurgery, Mbeya Zonal Referral Hospital and Mbeya University College of Medicine, University of Dar es Salaam, Box 419, Mbeya, Tanzania. 10. Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, 250012, Shandong, China. Kailiang-zhang@email.sdu.edu.cn. 11. Key Laboratory of Brain Function Remodeling, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, China. Kailiang-zhang@email.sdu.edu.cn. 12. Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, 250012, Shandong, China. ytfishn@126.com. 13. Key Laboratory of Brain Function Remodeling, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, China. ytfishn@126.com.
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 TCGA database and found that there was a significant negative correlation between the long noncoding RNA (lncRNA) HOTAIR and PPARα. Then, we explored the molecular mechanism by which lncRNA HOTAIR regulates PPARα in cell lines in vitro and in a nude mouse glioma model in vivo and explored the effect of the combined application of HOTAIR knockdown and fenofibrate treatment on glioma invasion. RESULTS: For the first time, it was shown that after knockdown of the expression of HOTAIR in gliomas, the expression of PPARα was significantly upregulated, and the invasion and proliferation ability of gliomas were obviously inhibited. Then, glioma cells were treated with both the PPARα agonist fenofibrate and si-HOTAIR, and the results showed that the proliferation and invasion of glioma cells were significantly inhibited. CONCLUSIONS: Our results suggest that HOTAIR can negatively regulate the expression of PPARα and that the combination of fenofibrate and si-HOTAIR treatment can significantly inhibit the progression of gliomas. This introduces new ideas for the treatment of gliomas.
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 TCGA database and found that there was a significant negative correlation between the long noncoding RNA (lncRNA) HOTAIR and PPARα. Then, we explored the molecular mechanism by which lncRNA HOTAIR regulates PPARα in cell lines in vitro and in a nude mouseglioma model in vivo and explored the effect of the combined application of HOTAIR knockdown and fenofibrate treatment on glioma invasion. RESULTS: For the first time, it was shown that after knockdown of the expression of HOTAIR in gliomas, the expression of PPARα was significantly upregulated, and the invasion and proliferation ability of gliomas were obviously inhibited. Then, glioma cells were treated with both the PPARα agonist fenofibrate and si-HOTAIR, and the results showed that the proliferation and invasion of glioma cells were significantly inhibited. CONCLUSIONS: Our results suggest that HOTAIR can negatively regulate the expression of PPARα and that the combination of fenofibrate and si-HOTAIR treatment can significantly inhibit the progression of gliomas. This introduces new ideas for the treatment of gliomas.
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