title: MicroRNA-17-92 cluster mediates the proliferation and survival of neural progenitor cells after stroke.
abstract: The role of microRNAs (miRNAs) in mediating adult neurogenesis after stroke has not been extensively studied. The present study investigated the function of the miR17-92 cluster in adult neural progenitor cells after experimental stroke. We found that stroke substantially up-regulated miR17-92 cluster expression in neural progenitor cells of the adult mouse. Overexpression of the miR17-92 cluster either in cultured ischemic neural progenitor cells or in the subventricular zone (SVZ) of ischemic animals significantly increased cell proliferation, whereas inhibition of individual members of the miR17-92 cluster, miR-18a and miR-19a, suppressed cell proliferation and increased cell death. The miR17-92 cluster mediated PTEN (phosphatase and tensin homolog) expression, which is a predicted target of the miR17-92 cluster. Addition of Sonic hedgehog (Shh) protein up-regulated miR17-92 expression and elevated c-Myc protein in ischemic neural progenitor cells, whereas blockade of the Shh signaling pathway down-regulated miR17-92 cluster expression and reduced c-Myc levels. Overexpression of c-Myc up-regulated miR17-92 cluster expression. Intraventricular infusion of Shh and a Shh receptor inhibitor, cyclopamine, to ischemic animals further elevated and suppressed, respectively, miR17-92 cluster expression in the SVZ. These data indicate that the miR17-92 cluster plays an important role in mediating neural progenitor cell function and that the Shh signaling pathway is involved in up-regulating miR17-92 cluster expression.
authors.affiliation: Department of Neurology, Henry Ford Health System, Detroit, Michigan 48202, USA. xsliu@neuro.hfh.edu
authors.forename: Xian Shuang
authors.initials: XS
authors.lastname: Liu
authors.forename: Michael
authors.initials: M
authors.lastname: Chopp
authors.forename: Xin Li
authors.initials: XL
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Ann
authors.initials: A
authors.lastname: Hozeska-Solgot
authors.forename: Tao
authors.initials: T
authors.lastname: Tang
authors.forename: Haifa
authors.initials: H
authors.lastname: Kassis
authors.forename: Rui Lan
authors.initials: RL
authors.lastname: Zhang
authors.forename: Charles
authors.initials: C
authors.lastname: Chen
authors.forename: Jennifer
authors.initials: J
authors.lastname: Xu
authors.forename: Zheng Gang
authors.initials: ZG
authors.lastname: Zhang
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002470:Cell Survival; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D053823:Hedgehog Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis*; D005810:Multigene Family; D009419:Nerve Tissue Proteins / Q000378:metabolism; D058953:Neural Stem Cells / Q000378:metabolism* / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D053823:Hedgehog Proteins; D035683:MicroRNAs; C489428:Myc protein, mouse; D009419:Nerve Tissue Proteins; D016271:Proto-Oncogene Proteins c-myc; C465570:Shh protein, mouse; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse
keywords: Apoptosis; MicroRNA; Neural Stem Cell; Proliferation; Sonic Hedgehog; Stroke; Subventricular Zone (SVZ)