期刊
ONCOTARGET
卷 1, 期 8, 页码 710-720出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.205
关键词
cancer; microRNA; Policomb group; glioblastoma; angiogenesis
资金
- Dutch Cancer Foundation
- Lion's Cancer Research Foundation
- Umea University, Sweden
- Stichting Translational Research CCA/VU University medical center
- Swedish Research Counsil
- NIH, National Cancer Institute, Center for Cancer Research
Background: Glioblastoma (GBM) is a malignant brain tumor with dismal prognosis. GBM patients have a median survival of less than 2 years. GBM is characterized by fast cell proliferation, infiltrative migration, and by the induction of angiogenesis. MicroRNAs and polycomb group (PcG) proteins have emerged as important regulators of gene expression. Methods: Here we determined that miR-101 is down-regulated in GBM, resulting in overexpression of the miR-101 target PcG protein EZH2, a histone methyltransferase affecting gene expression profiles in an epigenetic manner. Results: Inhibition of EZH2 in vitro by pre-miR-101, EZH2 siRNA, or small molecule DZNep, attenuated GBM cell growth, migration/invasion, and GBM-induced endothelial tubule formation. In addition, for each biological process we identified ontology-associated transcripts that significantly correlate with EZH2 expression. Inhibition of EZH2 in vivo by systemic DZNep administration in a U87-Fluc-mCherry GBM xenograft mouse imaging model resulted in reduced tumor growth. Conclusion: Our results indicate that EZH2 has a versatile function in GBM progression and that its overexpression is at least partly due to decreased miR-101 expression. Inhibition of EZH2 may be a potential therapeutic strategy to target GBM proliferation, migration, and angiogenesis.cancer, microRNA, Policomb group, glioblastoma, angiogenesis
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