title: Long non-coding RNA SNHG14 promotes microglia activation by regulating miR-145-5p/PLA2G4A in cerebral infarction.
abstract: Activated microglia cells (MCs) are able to release a large amount of inflammatory cytokines after ischemic stroke, which exacerbates neuron damage. In this study, we explored the functional involvement of long non-coding RNA (lncRNA) SNHG14 and its potential regulatory mechanism in the activation of MCs. The mouse model of middle cerebral artery occlusion (MCAO) and microglia cell model of oxygen/glucose deprivation (OGD) were made. The expression of SNHG14, miR-145-5p and PLA2G4A protein expression was determined by quantitative real time PCR and western blot, respectively. Dual-luciferase assay was used to verify the direct binding of miR-145-5p and PLA2G4A. Flow cytometry was applied to measure neurons' apoptosis. SNHG14 highly expressed in ischemic cerebral tissues and BV-2 cells after OGD treatment. SNHG14 knockdown could remarkably inhibit BV-2 cells activation induced by OGD; while SNHG14 overexpression significantly promoted BV-2 cells activation, showing an increase of TNF-α and NO production and neurons' apoptosis rate. Additionally, SNHG14 knockdown promoted the expression of miR-145-5p and reduced PLA2G4A. Contrarily, SNHG14 overexpression inhibited miR-145-5p expression and increased PLA2G4A. Moreover, miR-145-5p overexpression also reversed the effect of OGD on BV-2 cells activation. Bioinformatics analysis and dual-luciferase assay supported that SNHG14 could bind directly to miR-145-5p and miR-145-5p-binding site was existed on 3'-UTR of PLA2G4A. MiR-145-5p mimic reversed the increase of PLA2G4A and reduced the high levels of TNF-α and NO in BV-2 cells induced by SNHG14 overexpression. SNHG14 increased the expression of PLA2G4A by inhibition of miR-145-5p, which resulted in the activation of MCs in cerebral infarction.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China. Electronic address: qixu16125@163.com.
authors.forename: Xu
authors.initials: X
authors.lastname: Qi
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Shao
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Hongjing
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Delong
authors.initials: D
authors.lastname: Meng
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Huo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002544:Cerebral Infarction / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D054513:Group IV Phospholipases A2 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C543499:MIRN145a microRNA, mouse; D035683:MicroRNAs; C516390:Pla2g4a protein, mouse; D062085:RNA, Long Noncoding; D014409:Tumor Necrosis Factor-alpha; D054513:Group IV Phospholipases A2
keywords: PLA2G4A; SNHG14; miR-145-5p; microglia activation