Oncotarget

Research Papers:

PPARα, a predictor of patient survival in glioma, inhibits cell growth through the E2F1/miR-19a feedback loop

Yan Shi, Tao Tao, Ning Liu, WenKang Luan, Jin Qian, Rui Li, Qi Hu, Yan Wei, Junxia Zhang and Yongping You _

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Oncotarget. 2016; 7:84623-84633. https://doi.org/10.18632/oncotarget.13170

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Abstract

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

Correspondence to:

Yongping You, email: YYPL9@njmu.edu.cn

Junxia Zhang, email: zjx232@126.com

Keywords: PPARα, E2F1, miR-19a, RB, feedback loop

Received: March 19, 2016     Accepted: October 28, 2016     Published: November 07, 2016

ABSTRACT

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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