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Micro-RNA-128 (miRNA-128) down-regulation in glioblastoma targets ARP5 (ANGPTL6), Bmi-1 and E2F-3a, key regulators of brain cell proliferation

  • Laboratory Investigation - Human/Animal Tissue
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Abstract

High density micro-RNA (miRNA) arrays, fluorescent-reporter miRNA assay and Northern miRNA dot-blot analysis show that a brain-enriched miRNA-128 is significantly down-regulated in glioblastoma multiforme (GBM) and in GBM cell lines when compared to age-matched controls. The down-regulation of miRNA-128 was found to inversely correlate with WHO tumor grade. Three bioinformatics-verified miRNA-128 targets, angiopoietin-related growth factor protein 5 (ARP5; ANGPTL6), a transcription suppressor that promotes stem cell renewal and inhibits the expression of known tumor suppressor genes involved in senescence and differentiation, Bmi-1, and a transcription factor critical for the control of cell-cycle progression, E2F-3a, were found to be up-regulated. Addition of exogenous miRNA-128 to CRL-1690 and CRL-2610 GBM cell lines (a) restored ‘homeostatic’ ARP5 (ANGPTL6), Bmi-1 and E2F-3a expression, and (b) significantly decreased the proliferation of CRL-1690 and CRL-2610 cell lines. Our data suggests that down-regulation of miRNA-128 may contribute to glioma and GBM, in part, by coordinately up-regulating ARP5 (ANGPTL6), Bmi-1 and E2F-3a, resulting in the proliferation of undifferentiated GBM cells.

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Acknowledgments

Thanks are extended to Darlene Guillot and Aileen Pogue for expert technical assistance. This work was supported in part by a post-Katrina Translation Research Initiative (TRI) Grant from the Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. Part of this work was presented in abstract form at the Society for Neuro-oncology (SNO) Annual Meeting, New Orleans, LA October 22–24, 2009.

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Authors and Affiliations

  1. LSU Neuroscience Center & Department of Ophthalmology, Louisiana State University Health Science Center, New Orleans, LA, 70112, USA

    J. G. Cui, Y. Y. Li & W. J. Lukiw

  2. Department of Structural Biology, University of Pittsburgh, Pittsburgh, PA, 15260, USA

    Y. Zhao

  3. Department of Health Information Management, School of Biological Sciences, Louisiana Technical University, Ruston, LA, 71272, USA

    P. Sethi

  4. LSU Department of Neurosurgery, Louisiana State University Health Science Center, New Orleans, LA, 70112, USA

    A. Mahta & F. Culicchia

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  1. J. G. Cui
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  2. Y. Zhao
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  3. P. Sethi
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  4. Y. Y. Li
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  5. A. Mahta
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  6. F. Culicchia
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  7. W. J. Lukiw
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Correspondence to W. J. Lukiw.

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Cui, J.G., Zhao, Y., Sethi, P. et al. Micro-RNA-128 (miRNA-128) down-regulation in glioblastoma targets ARP5 (ANGPTL6), Bmi-1 and E2F-3a, key regulators of brain cell proliferation. J Neurooncol 98, 297–304 (2010). https://doi.org/10.1007/s11060-009-0077-0

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  • DOI: https://doi.org/10.1007/s11060-009-0077-0

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