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


ABSTRACT: Nuclear receptors such as peroxisome proliferator-activated receptor ? (PPAR?) are potential therapeutic targets. In this study, we found that PPAR? expression was lower in high grade gliomas and PPAR? was an independent prognostic factor in GBM patients. PPAR? 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 PPAR? expression. E2F1 knockdown up-regulated PPAR? 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, PPAR? repressed E2F1 via the p21 pathwayby modulating the transcriptional complexes containing E2F1 and pRB proteins. These results suggest that the E2F1/miR19a/PPAR? feedback loop is critical for glioma progression.

SUBMITTER: Shi Y 

PROVIDER: S-EPMC5356686 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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

Shi Yan Y   Tao Tao T   Liu Ning N   Luan WenKang W   Qian Jin J   Li Rui R   Hu Qi Q   Wei Yan Y   Zhang Junxia J   You Yongping Y  

Oncotarget 20161201 51


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 decrease  ...[more]

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