title: Genome-wide profiling identified a set of miRNAs that are differentially expressed in glioblastoma stem cells and normal neural stem cells.
abstract: A major challenge in cancer research field is to define molecular features that distinguish cancer stem cells from normal stem cells. In this study, we compared microRNA (miRNA) expression profiles in human glioblastoma stem cells and normal neural stem cells using combined microarray and deep sequencing analyses. These studies allowed us to identify a set of 10 miRNAs that are considerably up-regulated or down-regulated in glioblastoma stem cells. Among them, 5 miRNAs were further confirmed to have altered expression in three independent lines of glioblastoma stem cells by real-time RT-PCR analysis. Moreover, two of the miRNAs with increased expression in glioblastoma stem cells also exhibited elevated expression in glioblastoma patient tissues examined, while two miRNAs with decreased expression in glioblastoma stem cells displayed reduced expression in tumor tissues. Furthermore, we identified two oncogenes, NRAS and PIM3, as downstream targets of miR-124, one of the down-regulated miRNAs; and a tumor suppressor, CSMD1, as a downstream target of miR-10a and miR-10b, two of the up-regulated miRNAs. In summary, this study led to the identification of a set of miRNAs that are differentially expressed in glioblastoma stem cells and normal neural stem cells. Characterizing the role of these miRNAs in glioblastoma stem cells may lead to the development of miRNA-based therapies that specifically target tumor stem cells, but spare normal stem cells.
authors.affiliation: Department of Neurosciences, Center for Gene Expression and Drug Discovery, Cancer Center, Beckman Research Institute of City of Hope, Duarte, California, USA.
authors.forename: Ming-Fei
authors.initials: MF
authors.lastname: Lang
authors.forename: Su
authors.initials: S
authors.lastname: Yang
authors.forename: Chunnian
authors.initials: C
authors.lastname: Zhao
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Sun
authors.forename: Kiyohito
authors.initials: K
authors.lastname: Murai
authors.forename: Xiwei
authors.initials: X
authors.lastname: Wu
authors.forename: Jinhui
authors.initials: J
authors.lastname: Wang
authors.forename: Hanlin
authors.initials: H
authors.lastname: Gao
authors.forename: Christine E
authors.initials: CE
authors.lastname: Brown
authors.forename: Xiaoxuan
authors.initials: X
authors.lastname: Liu
authors.forename: Jiehua
authors.initials: J
authors.lastname: Zhou
authors.forename: Ling
authors.initials: L
authors.lastname: Peng
authors.forename: John J
authors.initials: JJ
authors.lastname: Rossi
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Shi
mesh_terms: D045744:Cell Line, Tumor; D015536:Down-Regulation; D020869:Gene Expression Profiling; D016147:Genes, Tumor Suppressor; D023281:Genomics; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D058953:Neural Stem Cells / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D015203:Reproducibility of Results; D017423:Sequence Analysis, RNA; D015854:Up-Regulation
chemical_list: D035683:MicroRNAs