title: Neuroprotective effects of miR-27a against traumatic brain injury via suppressing FoxO3a-mediated neuronal autophagy.
abstract: MicroRNA-27a (miR-27a) has been reported to be a brain-specific miRNA and aberrantly expressed in the brain suffered from traumatic brain injury (TBI). The present study is designed to investigate the potential role and molecular mechanism of miR-27a in the pathogenesis of TBI. The level of miR-27a in brain was manipulated by intracerebroventricular injection of lentiviral-encoding miR-27a before TBI induction. Real-time PCR was used to detected miR-27a and Forkhead box O3a (FoxO3a) levels in the hippocampus. Then, we evaluated the impact of miR-27a overexpression on neurological function, brain edema, lesion volume and neuronal autophagy after TBI. The blinding of miR-27a to the 3'UTR of FoxO3a mRNA and its effects on FoxO3a translation were analyzed by luciferase reporter assay and Western blot. The downregulation of miR-27a and the increase in FoxO3a level were observed in the hippocampus post-TBI. Overexpression of miR-27a significantly attenuated neurological deficits and brain injury, especially suppressed autophagic activation after TBI. Furthermore, we identified that miR-27a directly targeted the FoxO3a 3'UTR region to reduced FoxO3a protein expression. Knockdown of FoxO3a significantly reversed high levels of autophagy-related genes induced by TBI. Taken together, Overexpression of miR-27a may protect against brain injury via suppressing FoxO3a-mediated neuronal autophagy following TBI.
authors.affiliation: Department of Interventional Neuroradiology, Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Liqian
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Histology and Embryology, School of Basic Medical Science, North China University of Science and Technology, Hebei, Tangshan 063000, China.
authors.forename: Manman
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Histology and Embryology, School of Basic Medical Science, North China University of Science and Technology, Hebei, Tangshan 063000, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Interventional Neuroradiology, Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Liu
authors.affiliation: Department of Interventional Neuroradiology, Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Lv
authors.affiliation: Department of Interventional Neuroradiology, Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Youxiang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Interventional Neuroradiology, Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Xinjian
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Interventional Neuroradiology, Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China. Electronic address: zhongxuewu@yeah.net.
authors.forename: Zhongxue
authors.initials: Z
authors.lastname: Wu
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001343:Autophagy; D001665:Binding Sites; D001929:Brain Edema / Q000473:pathology; D000070642:Brain Injuries, Traumatic / Q000378:metabolism*; D019295:Computational Biology; D000071316:Forkhead Box Protein O3 / Q000378:metabolism*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006624:Hippocampus / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D000066829:Neuroprotection; D014176:Protein Biosynthesis; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D020413:3' Untranslated Regions; C499515:FOXO3 protein, rat; D000071316:Forkhead Box Protein O3; C000594049:MIRN27 microRNA, rat; D035683:MicroRNAs
keywords: Autophagy; FoxO3a; Hippocampus; MicroRNA-27a; Traumatic brain injury