title: MicroRNA-25 Negatively Regulates Cerebral Ischemia/Reperfusion Injury-Induced Cell Apoptosis Through Fas/FasL Pathway.
abstract: MicroRNA-25 (miR-25) has been reported to be a major miRNA marker in neural cells and is strongly expressed in ischemic brain tissues. However, the precise mechanism and effect of miR-25 in cerebral ischemia/reperfusion (I/R) injury needs further investigations. In the present study, the oxygen-glucose deprivation (OGD) model was constructed in human SH-SY5Y and IMR-32 cells to mimic I/R injury and to evaluate the role of miR-25 in regulating OGD/reperfusion (OGDR)-induced cell apoptosis. We found that miR-25 was downregulated in the OGDR model. Overexpression of miR-25 via miRNA-mimics transfection remarkably inhibited OGDR-induced cell apoptosis. Moreover, Fas was predicted as a target gene of miR-25 through bioinformatic analysis. The interaction between miR-25 and 3'-untranslated region (UTR) of Fas mRNA was confirmed by dual-luciferase reporter assay. Fas protein expression was downregulated by miR-25 overexpression in OGDR model. Subsequently, the small interfering RNA (siRNA)-mediated knockdown of Fas expression also inhibited cell apoptosis induced by OGDR model; in contrast, Fas overexpression abrogated the protective effects of miR-25 on OGDR-induced cells. Taken together, our results indicate that the upregulation of miR-25 inhibits cerebral I/R injury-induced apoptosis through downregulating Fas/FasL, which will provide a promising therapeutic target.
authors.affiliation: Department of Human Anatomy, Xi'an Medical University, No. 1, Xinwang Road, Weiyang District, Xi'an, 710021, People's Republic of China.
authors.forename: Jun-Feng
authors.initials: JF
authors.lastname: Zhang
authors.affiliation: Department of Human Anatomy, Xi'an Medical University, No. 1, Xinwang Road, Weiyang District, Xi'an, 710021, People's Republic of China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Shi
authors.affiliation: Department of Human Anatomy, Xi'an Medical University, No. 1, Xinwang Road, Weiyang District, Xi'an, 710021, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Human Anatomy, Xi'an Medical University, No. 1, Xinwang Road, Weiyang District, Xi'an, 710021, People's Republic of China.
authors.forename: Zhao-Hua
authors.initials: ZH
authors.lastname: Zhao
authors.affiliation: Department of Human Anatomy, Xi'an Medical University, No. 1, Xinwang Road, Weiyang District, Xi'an, 710021, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Liang
authors.affiliation: Department of Human Anatomy, Xi'an Medical University, No. 1, Xinwang Road, Weiyang District, Xi'an, 710021, People's Republic of China. xx_anato@163.com.
authors.forename: Xi
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, People's Republic of China. lingyu_zh@126.com.
authors.forename: Ling-Yu
authors.initials: LY
authors.lastname: Zhao
authors.affiliation: Department of Human Anatomy & Histo-embryology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, People's Republic of China.
authors.forename: Peng-Bo
authors.initials: PB
authors.lastname: Yang
authors.affiliation: Department of Human Anatomy & Histo-embryology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, People's Republic of China.
authors.forename: Jian-Shui
authors.initials: JS
authors.lastname: Zhang
authors.affiliation: College of Life Sciences, Shaanxi Normal University, Xi'an, 710062, People's Republic of China.
authors.forename: Ying-Fang
authors.initials: YF
authors.lastname: Tian
mesh_terms: D017209:Apoptosis; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D015536:Down-Regulation; D053222:Fas Ligand Protein / Q000378:metabolism; D005947:Glucose / Q000172:deficiency*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D015398:Signal Transduction; D019014:fas Receptor / Q000378:metabolism
chemical_list: C491901:FAS protein, human; D053222:Fas Ligand Protein; C543351:MIRN25 microRNA, human; D035683:MicroRNAs; D019014:fas Receptor; D005947:Glucose; D010100:Oxygen
keywords: Apoptosis; Fas/FasL; Ischemia/reperfusion injury; microRNA-25