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cells, expression, cell, differentiation, stem, gbm, pubmed, article, tumor, google, scholar, human, mirnas, cas, mirna, figure, brain, microrna, glioblastoma, transfection, mouse, neuronal, growth, file, additional, cdk, adult, tumors, lines, studies, cancer, multiforme, cycle, neural, hours, relative, control, tuj, proliferation, results, central, tissue, fold, factor, analyses, days, induce, primary, protein, treatment,

Topics {✒️}

cyclin-dependent kinase 6-3'utr d-type cyclin-dependent kinases 1 mg/ml poly-d-lysine wt cdk6-3'utr anti-neural rest/scp1 pathway 3'utr reporter assays open access article alternative pre-mrna splicing low-adherent tissue-culture dishes fluorescence-activated cell sorter s100β-v-erbb tumors lukas rv cel-mir-67-negative-control mimics cyclin-dependent kinase 6 central nervous system glioblastoma-multiforme tumor cells myc-activated microrna cluster fluorescence-activated cell sorting pre-publication history alexa594-conjugated secondary antibodies pre-coated culture dishes transgenic mouse expressing dna stain 7-amino-actinomycin ultra-low adherent plates cell-cycle inhibitor p27 mouse embryonic stem serum-cultured cell lines neural stem cells microrna-producing enzyme dicer1 article download pdf double-stranded rna oligonucleotides rna interference-based mechanisms pmir-report vectors rna-induced silencing complex growth-factor-deprived mnscs growth-factor-deprived hgscs uc-genentech discovery grant human astroblastomas [32] pmir-report vector cell cycle arrest cell lines derived v-erbb transgene tumor stem cells neural cell specification high-grade astrocytoma-micrornas world health organization growth factor signaling blood brain barrier stem cell division high-glucose dmem supplemented

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         headline:miR-124 and miR-137 inhibit proliferation of glioblastoma multiforme cells and induce differentiation of brain tumor stem cells
         description:Glioblastoma multiforme (GBM) is an invariably fatal central nervous system tumor despite treatment with surgery, radiation, and chemotherapy. Further insights into the molecular and cellular mechanisms that drive GBM formation are required to improve patient outcome. MicroRNAs are emerging as important regulators of cellular differentiation and proliferation, and have been implicated in the etiology of a variety of cancers, yet the role of microRNAs in GBM remains poorly understood. In this study, we investigated the role of microRNAs in regulating the differentiation and proliferation of neural stem cells and glioblastoma-multiforme tumor cells. We used quantitative RT-PCR to assess microRNA expression in high-grade astrocytomas and adult mouse neural stem cells. To assess the function of candidate microRNAs in high-grade astrocytomas, we transfected miR mimics to cultured-mouse neural stem cells, -mouse oligodendroglioma-derived stem cells, -human glioblastoma multiforme-derived stem cells and -glioblastoma multiforme cell lines. Cellular differentiation was assessed by immunostaining, and cellular proliferation was determined using fluorescence-activated cell sorting. Our studies revealed that expression levels of microRNA-124 and microRNA-137 were significantly decreased in anaplastic astrocytomas (World Health Organization grade III) and glioblastoma multiforme (World Health Organization grade IV) relative to non-neoplastic brain tissue (P < 0.01), and were increased 8- to 20-fold during differentiation of cultured mouse neural stem cells following growth factor withdrawal. Expression of microRNA-137 was increased 3- to 12-fold in glioblastoma multiforme cell lines U87 and U251 following inhibition of DNA methylation with 5-aza-2'-deoxycytidine (5-aza-dC). Transfection of microRNA-124 or microRNA-137 induced morphological changes and marker expressions consistent with neuronal differentiation in mouse neural stem cells, mouse oligodendroglioma-derived stem cells derived from S100β-v-erbB tumors and cluster of differentiation 133+ human glioblastoma multiforme-derived stem cells (SF6969). Transfection of microRNA-124 or microRNA-137 also induced G1 cell cycle arrest in U251 and SF6969 glioblastoma multiforme cells, which was associated with decreased expression of cyclin-dependent kinase 6 and phosphorylated retinoblastoma (pSer 807/811) proteins. microRNA-124 and microRNA-137 induce differentiation of adult mouse neural stem cells, mouse oligodendroglioma-derived stem cells and human glioblastoma multiforme-derived stem cells and induce glioblastoma multiforme cell cycle arrest. These results suggest that targeted delivery of microRNA-124 and/or microRNA-137 to glioblastoma multiforme tumor cells may be therapeutically efficacious for the treatment of this disease.
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      headline:miR-124 and miR-137 inhibit proliferation of glioblastoma multiforme cells and induce differentiation of brain tumor stem cells
      description:Glioblastoma multiforme (GBM) is an invariably fatal central nervous system tumor despite treatment with surgery, radiation, and chemotherapy. Further insights into the molecular and cellular mechanisms that drive GBM formation are required to improve patient outcome. MicroRNAs are emerging as important regulators of cellular differentiation and proliferation, and have been implicated in the etiology of a variety of cancers, yet the role of microRNAs in GBM remains poorly understood. In this study, we investigated the role of microRNAs in regulating the differentiation and proliferation of neural stem cells and glioblastoma-multiforme tumor cells. We used quantitative RT-PCR to assess microRNA expression in high-grade astrocytomas and adult mouse neural stem cells. To assess the function of candidate microRNAs in high-grade astrocytomas, we transfected miR mimics to cultured-mouse neural stem cells, -mouse oligodendroglioma-derived stem cells, -human glioblastoma multiforme-derived stem cells and -glioblastoma multiforme cell lines. Cellular differentiation was assessed by immunostaining, and cellular proliferation was determined using fluorescence-activated cell sorting. Our studies revealed that expression levels of microRNA-124 and microRNA-137 were significantly decreased in anaplastic astrocytomas (World Health Organization grade III) and glioblastoma multiforme (World Health Organization grade IV) relative to non-neoplastic brain tissue (P < 0.01), and were increased 8- to 20-fold during differentiation of cultured mouse neural stem cells following growth factor withdrawal. Expression of microRNA-137 was increased 3- to 12-fold in glioblastoma multiforme cell lines U87 and U251 following inhibition of DNA methylation with 5-aza-2'-deoxycytidine (5-aza-dC). Transfection of microRNA-124 or microRNA-137 induced morphological changes and marker expressions consistent with neuronal differentiation in mouse neural stem cells, mouse oligodendroglioma-derived stem cells derived from S100β-v-erbB tumors and cluster of differentiation 133+ human glioblastoma multiforme-derived stem cells (SF6969). Transfection of microRNA-124 or microRNA-137 also induced G1 cell cycle arrest in U251 and SF6969 glioblastoma multiforme cells, which was associated with decreased expression of cyclin-dependent kinase 6 and phosphorylated retinoblastoma (pSer 807/811) proteins. microRNA-124 and microRNA-137 induce differentiation of adult mouse neural stem cells, mouse oligodendroglioma-derived stem cells and human glioblastoma multiforme-derived stem cells and induce glioblastoma multiforme cell cycle arrest. These results suggest that targeted delivery of microRNA-124 and/or microRNA-137 to glioblastoma multiforme tumor cells may be therapeutically efficacious for the treatment of this disease.
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         Tumor Stem Cell
         Adult NSCs
         Astroblastomas
         Mouse Neural Stem Cell
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         Biomedicine
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      name:William A Weiss
      affiliation:
            name:University of California San Francisco
            address:
               name:Department of Neurology, University of California San Francisco, San Francisco, USA
               type:PostalAddress
            type:Organization
            name:University of California San Francisco
            address:
               name:Department of Pediatrics, University of California San Francisco, San Francisco, USA
               type:PostalAddress
            type:Organization
      name:Arturo Alvarez-Buylla
      affiliation:
            name:University of California San Francisco
            address:
               name:Department of Neurological Surgery, University of California San Francisco, San Francisco, USA
               type:PostalAddress
            type:Organization
      name:J Graeme Hodgson
      affiliation:
            name:University of California San Francisco
            address:
               name:Department of Neurological Surgery, University of California San Francisco, San Francisco, USA
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Neurological Surgery, University of California San Francisco, San Francisco, USA
      name:Department of Neurological Surgery, University of California San Francisco, San Francisco, USA
      name:Department of Neurological Surgery, University of California San Francisco, San Francisco, USA
      name:Department of Neurology, University of California San Francisco, San Francisco, USA
      name:Department of Pediatrics, University of California San Francisco, San Francisco, USA
      name:Department of Neurological Surgery, University of California San Francisco, San Francisco, USA
      name:Department of Neurological Surgery, University of California San Francisco, San Francisco, USA
      name:Department of Pathology, University of California San Francisco, San Francisco, USA
      name:Applied Biosystems, Foster City, USA
      name:Department of Neurological Surgery, University of California San Francisco, San Francisco, USA
      name:Department of Neurological Surgery, University of California San Francisco, San Francisco, USA
      name:Department of Neurological Surgery, University of California San Francisco, San Francisco, USA
      name:Department of Neurology, University of California San Francisco, San Francisco, USA
      name:Department of Pediatrics, University of California San Francisco, San Francisco, USA
      name:Department of Neurological Surgery, University of California San Francisco, San Francisco, USA
      name:Department of Neurological Surgery, University of California San Francisco, San Francisco, USA

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