title: microRNA-200a silencing protects neural stem cells against cerebral ischemia/reperfusion injury.
abstract: Neural stem cells (NSCs) play major roles in neurological recovery after cerebral infarction (CI). This study was trying to investigate whether miR-200a, a vital regulator in cell proliferation, migration and apoptosis, also has a role in oxygen-glucose deprivation/reperfusion (OGD/R) injured NSCs. In this study, primary NSCs were subjected to OGD/R conditions to mimic an in vitro CI model. Before OGD/R induction, NSCs were transfected with vector or shRNA against miR-200a to overexpress or suppress miR-200a expression. The changes in cell viability, apoptosis, migration, the expression of c-Myc, and the phosphorylation of STAT1, STAT3 and MAPK were respectively assessed. Inhibitors of STAT1/3 and MAPK, i.e., Nifuroxazide and BIRB 796, were used to administrate miR-200a-silenced NSCs, and the expressions of above mentioned proteins were detected. After OGD/R exposure, miR-200a was up-regulated in NSCs (P < 0.001). miR-200a silencing alleviated OGD/R-induced the decrease of cell viability and migration (P < 0.01); meanwhile, alleviated OGD/R-induced apoptosis via reducing Bax/Bcl-2 ratio and down-regulating p53 and cytochrome c (P < 0.01 or P < 0.001). c-Myc, p-STAT1, p-STAT3, p-MAPK were all negatively regulated by miR-200a (P < 0.01 or P < 0.001); more important, the increase of c-Myc induced by miR-200a silencing was abolished by Nifuroxazide or BIRB 796 (P < 0.01 or P < 0.001). These data indicate miR-200a silencing protects NSCs from OGD/R-induced injury, possibly via regulating the STATs/c-Myc and MAPK/c-Myc signalings.
authors.affiliation: Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Shaofeng
authors.initials: S
authors.lastname: Shui
authors.affiliation: Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Xinwei
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Guo
authors.affiliation: Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Tengfei
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D002545:Brain Ischemia / Q000517:prevention & control*; D020935:MAP Kinase Signaling System / Q000502:physiology; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D058953:Neural Stem Cells / Q000502:physiology*; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology; D060888:Real-Time Polymerase Chain Reaction; D015427:Reperfusion Injury / Q000517:prevention & control*
chemical_list: D035683:MicroRNAs; C543719:Mirn200 microRNA, mouse; C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc