miR-101 is down-regulated in glioblastoma resulting in EZH2-induced proliferation, migration, and angiogenesis
2010 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 1, no 8, 710-720 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
Impact Journals LLC , 2010. Vol. 1, no 8, 710-720 p.
cancer, microRNA, Policomb group, glioblastoma, angiogenesis
Cancer and Oncology
IdentifiersURN: urn:nbn:se:umu:diva-55703ISI: 000293506500003PubMedID: 21321380OAI: oai:DiVA.org:umu-55703DiVA: diva2:528764