title: Expression of miR-124 inhibits growth of medulloblastoma cells.
abstract: Medulloblastoma is the most common malignant brain tumor in children, and a substantial number of patients die as a result of tumor progression. Overexpression of CDK6 is present in approximately one-third of medulloblastomas and is an independent poor prognostic marker for this disease. MicroRNA (miR)-124 inhibits expression of CDK6 and prevents proliferation of glioblastoma and medulloblastoma cells in vitro. We examined the effects of miR-124 overexpression on medulloblastoma cells both in vitro and in vivo and compared cell lines that have low and high CDK6 expression. MiR-124 overexpression inhibits the proliferation of medulloblastoma cells, and this effect is mediated mostly through the action of miR-124 upon CDK6. We further show that induced expression of miR-124 potently inhibits growth of medulloblastoma xenograft tumors in rodents. Further testing of miR-124 will help define the ultimate therapeutic potential of preclinical models of medulloblastoma in conjunction with various delivery strategies for treatment.
authors.affiliation: Brain Tumor Research Center, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California 94143, USA.
authors.forename: Joachim
authors.initials: J
authors.lastname: Silber
authors.forename: Rintaro
authors.initials: R
authors.lastname: Hashizume
authors.forename: Tristan
authors.initials: T
authors.lastname: Felix
authors.forename: Sujatmi
authors.initials: S
authors.lastname: Hariono
authors.forename: Mamie
authors.initials: M
authors.lastname: Yu
authors.forename: Mitchel S
authors.initials: MS
authors.lastname: Berger
authors.forename: Jason T
authors.initials: JT
authors.lastname: Huse
authors.forename: Scott R
authors.initials: SR
authors.lastname: VandenBerg
authors.forename: C David
authors.initials: CD
authors.lastname: James
authors.forename: J Graeme
authors.initials: JG
authors.lastname: Hodgson
authors.forename: Nalin
authors.initials: N
authors.lastname: Gupta
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002528:Cerebellar Neoplasms / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008527:Medulloblastoma / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C509207:MIRN124 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger