title: MicroRNA-210 targets antiapoptotic Bcl-2 expression and mediates hypoxia-induced apoptosis of neuroblastoma cells.
abstract: MicroRNAs (miRNAs) can regulate cell survival and death by targeting apoptosis-related gene expression. miR-210 is one of the most hypoxia-sensitive miRNAs. In this study, we evaluated the roles of miR-210 in hypoxia-induced insults to neural cells. Treatment of neuro-2a cells with oxygen/glucose deprivation (OGD) induced cell apoptosis in a time-dependent manner. In parallel, OGD time-dependently increased cellular miR-210 levels. Knocking down miR-210 expression using specific antisenses significantly attenuated OGD-induced neural apoptosis. Concurrently, OGD increased hypoxia-inducible factor (HIF)-1α mRNA and protein syntheses. Pretreatment with YC-1, an inhibitor of HIF-1α, reduced OGD-caused cell death. Sequentially, OGD specifically decreased antiapoptotic Bcl-2 mRNA and protein levels in neuro-2a cells. A search by a bioinformatic approach revealed that miR-210-specific binding elements exist in the 3'-untranslated region of Bcl-2 mRNA. Application of miR-210 antisenses simultaneously alleviated OGD-involved inhibition of Bcl-2 mRNA expression. In comparison, overexpression of miR-210 synergistically diminished OGD-caused inhibition of Bcl-2 mRNA expression and consequently induced greater cellular insults. Taken together, this study shows that OGD can induce miR-210 expression through activating HIF-1α. And miR-210 can mediate hypoxia-induced neural apoptosis by targeting Bcl-2.
authors.affiliation: Department of Neurosurgery, Chi-Mei Medical Center, Tainan, Taiwan.
authors.forename: Chung-Ching
authors.initials: CC
authors.lastname: Chio
authors.forename: Jia-Wei
authors.initials: JW
authors.lastname: Lin
authors.forename: Heien-An
authors.initials: HA
authors.lastname: Cheng
authors.forename: Wen-Ta
authors.initials: WT
authors.lastname: Chiu
authors.forename: Yuan-Hung
authors.initials: YH
authors.lastname: Wang
authors.forename: Jhi-Joung
authors.initials: JJ
authors.lastname: Wang
authors.forename: Chung-Hsi
authors.initials: CH
authors.lastname: Hsing
authors.forename: Ruei-Ming
authors.initials: RM
authors.lastname: Chen
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001665:Binding Sites; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002470:Cell Survival; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D005947:Glucose / Q000172:deficiency; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D007191:Indazoles / Q000494:pharmacology; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010100:Oxygen / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D013997:Time Factors; D014162:Transfection
chemical_list: D020413:3' Untranslated Regions; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007191:Indazoles; C549325:MIRN210 microRNA, mouse; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; C052617:Bcl2 protein, mouse; C090937:3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole; D005947:Glucose; D010100:Oxygen