title: Impact of microRNA-134 on neural cell survival against ischemic injury in primary cultured neuronal cells and mouse brain with ischemic stroke by targeting HSPA12B.
abstract: As a newly discovered member of the HSP70 family, heat shock protein A12B (HSPA12B) is involved in brain ischemic injury. According to our previous study, microRNA-134 (miR-134) could target HSPA12B by binding to its 3'-untranslated region (UTR). However, the regulation of miR-134 on HSPA12B and their role in protecting neuronal cells from ischemic injury are unclear. In this study, the miR-134 expression level was manipulated, and the HSPA12B protein levels were also determined in oxygen-glucose deprivation (OGD)-treated primary cultured neuronal cells in vitro and mouse brain after middle cerebral artery occlusion (MCAO)-induced ischemic stroke in vivo. The results showed that miR-134 expression levels increased in primary cultured neuronal cells and mouse brain from 12h to 7 day reoxygenation/reperfusion after 1h OGD or 1h MCAO treatment. miR-134 overexpression promoted neuronal cell death and apoptosis by decreasing HSPA12B protein levels. Conversely, downregulating miR-134 reduced neuronal cell death and apoptosis by enhancing HSPA12B protein levels. Also, HSPA12B siRNA could block miR-134 inhibitor-mediated neuroprotection against OGD-induced neuronal cell injury in vitro. Taken together, miR-134 might influence neuronal cell survival against ischemic injury in primary cultured neuronal cells and mouse brain with ischemic stroke by negatively modulating HSPA12B protein expression in a posttranscriptional manner.
authors.affiliation: Department of Anesthesiology, Weifang Medical University, Weifang City 261053, Shangdong Province, PR China.
authors.forename: Wenying
authors.initials: W
authors.lastname: Chi
authors.affiliation: Department of Anesthesiology, Shandong University Affiliated Jinan City Central Hospital, Jinan 250013, PR China. Electronic address: mfj15318816233@163.com.
authors.forename: Fanjun
authors.initials: F
authors.lastname: Meng
authors.affiliation: Department of Anesthesiology, Shandong University Affiliated Jinan City Central Hospital, Jinan 250013, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Burn Surgery, Shandong University Affiliated Jinan City Central Hospital, Jinan 250013, PR China.
authors.forename: Peilong
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Weifang Medical University, Weifang City 261053, Shangdong Province, PR China.
authors.forename: Guizhi
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Shandong University Affiliated Jinan City Central Hospital, Jinan 250013, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Cheng
authors.affiliation: Department of Neurobiology and Beijing Institute for Brain Disorders, Capital Medical University, Beijing 100069, PR China.
authors.forename: Song
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Neurobiology and Beijing Institute for Brain Disorders, Capital Medical University, Beijing 100069, PR China. Electronic address: junfali@ccmu.edu.cn.
authors.forename: Junfa
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology*; D016923:Cell Death; D015687:Cell Hypoxia / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005947:Glucose / Q000172:deficiency; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D020244:Infarction, Middle Cerebral Artery; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D034741:RNA, Small Interfering; D020521:Stroke / Q000473:pathology / Q000503:physiopathology*
chemical_list: D018840:HSP70 Heat-Shock Proteins; C513783:HSPA12B protein, mouse; D035683:MicroRNAs; C551912:Mirn134 microRNA, mouse; D034741:RNA, Small Interfering; D005947:Glucose
keywords: Heat shock protein A12B (HSPA12B); Ischemic stroke; MicroRNA-134 (miR-134); Middle cerebral artery occlusion (MCAO); Oxygen-glucose deprivation (OGD)