Upregulation of Peroxisome Proliferator Activated Receptor-gamma in Mesenchymal Glioblastoma Subtype
Tuyen N. M. Hua1, 2, Yangsik Jeong1, 2 and Jong-Whan Choi1, * 1Department of Biochemistry, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do, Republic of Korea 2Department of Global Medical Science, Institute of Lifestyle Medicine, Nuclear Receptor Research Consortium, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do, Republic of Korea *Corresponding Author
Glioblastoma (GBM) heterogeneity is characterized by four subtypes including proneural, neural, classical and mesenchymal subtypes with distinct activated signaling pathways. Among them, proneural and mesenchymal subtypes are recognized to have mutually exclusive gene signatures. Compared to proneural subtype, mesenchymal GBM is responsible for tumor recurrence and drug resistance. Here we report the upregulation of peroxisome proliferator activated receptor-gamma (PPAR) particularly in mesenchymal subtype of GBM. Firstly, by RNA-seq data analysis, we found that PPAR is the most upregulated nuclear receptor in mesenchymal compared to proneural subtype. Using patient-derived glioblastoma stem cells (GSCs), we confirmed that mRNA and protein level of PPAR were significantly higher in mesenchymal GBM. High expression of PPAR in mesenchymal GBM was further demonstrated by available transcriptome microarray and The Cancer Genome Atlas glioblastoma database analysis. Since mesenchymal GBM is associated with poor prognosis, we also found PPAR upregulation links to poor overall survival and disease free survival of GBM patients. Collectively, our data here provided the evidence that PPAR upregulation could be one of the signatures for mesenchymal GBM, which may be exploited as the targeted treatment for this fatal disease.
This work was financially supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (NRF-2016R1D1A3B03930581 to YS Jeong), Medical Research Center Program (2017R1A5A2015369), and a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI17C0039).
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