PPARα, a predictor of patient survival in glioma, inhibits cell growth through the E2F1/miR-19a feedback loop
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Yan Shi1,*, Tao Tao1,*, Ning Liu1,*, WenKang Luan1,*, Jin Qian1,2, Rui Li1, Qi Hu1, Yan Wei1, Junxia Zhang1, Yongping You1
1Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
2Department of Neurosurgery, People’s Hospital of Xuancheng City, Anhui, China
*These authors contributed equally to this work
Yongping You, email: [email protected]
Junxia Zhang, email: [email protected]
Keywords: PPARα, E2F1, miR-19a, RB, feedback loop
Received: March 19, 2016 Accepted: October 28, 2016 Published: November 07, 2016
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.
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