PPARα, a predictor of patient survival in glioma, inhibits cell growth through the E2F1/miR-19a feedback loop.
Nuclear receptors such as peroxisome proliferator-activated receptor α (PPARα) are potential therapeutic targets. In this study, we found that PPARα expression was lower in high grade gliomas and PPARα was an independent prognostic factor in GBM patients. PPARα agonism or overexpression inhibited glioma cell proliferation, invasion, and aerobic glycolysis as well as suppressed glioma growth in an orthotopic model. Bioinformatic analysis and luciferase reporter assays showed that miR-19a decreased PPARα expression. E2F1 knockdown up-regulated PPARα and inhibited cell proliferation, invasion, and aerobic glycolysis, but this activity was blocked by miR-19a. Knockdown of E2F1 decreased miR-19a by inhibiting the miR-19a promoter. Moreover, PPARα repressed E2F1 via the p21 pathwayby modulating the transcriptional complexes containing E2F1 and pRB proteins. These results suggest that the E2F1/miR19a/PPARα feedback loop is critical for glioma progression.
Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Yan
Y
Shi
Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Tao
T
Tao
Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Ning
N
Liu
Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
WenKang
W
Luan
Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.|Department of Neurosurgery, People's Hospital of Xuancheng City, Anhui, China.
Jin
J
Qian
Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Rui
R
Li
Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Qi
Q
Hu
Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Yan
Y
Wei
Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Junxia
J
Zhang
Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Yongping
Y
You
D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D063646:Carcinogenesis; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D050687:E2F1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D025461:Feedback, Physiological; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009367:Neoplasm Staging; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C549214:MIRN19A microRNA, human; D035683:MicroRNAs; D047493:PPAR alpha; D034741:RNA, Small Interfering
E2F1; PPARα; RB; feedback loop; miR-19a