Abstract 4195: Peroxisome proliferator-activated receptor α is regulated by E2F1-induced miR-19a in a feedback loop in glioma progression

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA The peroxisome proliferator-activated receptor α (PPARα) is a nuclear receptor, which belongs to the super-family of steroid hormone receptor. To date, the biologic function of PPARα in human cancers is still controversial and needs further investigation. In our study, we explored the clinical feature, biological function and potential mechanism of PPARα in glioma. PPARα expression was significant lower in high grade tissues than low grade tissues in whole genome gene profiling of 158 glioma tissues. PPARα activation using fenofibrate inhibited glioma cells proliferation, invasion and aerobic glycolysis. Further, PPARα was a direct target of miR-19a and miR-19a was modulated by E2F1 at transcriptional level. Moreover, PPARα activation repressed E2F1 activation by modulating transcriptional complexes formed with E2F1 and pRB proteins. Finally, we confirmed PPARα/E2F1/ miR-19a feedback loop in vivo using nude mouse glioma xenograft and human glioma tissues. To our knowledge, it is first time to demonstrate that PPARα regulates glioma development by E2F1-induced miR-19a in a feedback loop and provide important clues for understanding the key roles of PPARα functional network in glioma. Note: This abstract was not presented at the meeting. Citation Format: Junxia Zhang, Yan Shi, Yingyi Wang, Wenkang Luan, Yongping You. Peroxisome proliferator-activated receptor α is regulated by E2F1-induced miR-19a in a feedback loop in glioma progression. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4195. doi:10.1158/1538-7445.AM2014-4195