Micro-RNA-128 (miRNA-128) down-regulation in glioblastoma targets ARP5 (ANGPTL6), Bmi-1 and E2F-3a,key regulators of brain cell proliferation |
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| Authors: | J. G. Cui Y. Zhao P. Sethi Y. Y. Li A. Mahta F. Culicchia W. J. Lukiw |
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| Affiliation: | (1) LSU Neuroscience Center & Department of Ophthalmology, Louisiana State University Health Science Center, New Orleans, LA 70112, USA;(2) Department of Structural Biology, University of Pittsburgh, Pittsburgh, PA 15260, USA;(3) Department of Health Information Management, School of Biological Sciences, Louisiana Technical University, Ruston, LA 71272, USA;(4) LSU Department of Neurosurgery, Louisiana State University Health Science Center, New Orleans, LA 70112, USA; |
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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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