title: miR-210 suppresses BNIP3 to protect against the apoptosis of neural progenitor cells.
abstract: MiR-210 is a hypoxia-inducible factor (HIF)-1 target gene and is the most consistently and predominantly upregulated miRNA in response to hypoxia in various cancer cell lines. Our recent study shows that hypoxia increased miR-210 expression in neural progenitor cells (NPCs) in a time-dependent manner. However, the role of miR-210 in NPCs remains unknown. Following the identification of the miR-210 putative target genes, we demonstrated that the Bcl-2 adenovirus E1B 19kDa-interacting protein 3 (BNIP3), which is regulated by HIF-1 and activates cell death, is regulated by miR-210 in NPCs under hypoxia. Moreover, the over-expression of miR-210 decreased apoptosis in NPCs, and the inhibition of miR-210 expression remarkably increased the number of TUNEL-positive NPCs by 30% in response to hypoxia. Importantly, miR-210 mimics reduced both BNIP3 protein expression and the translocation of AIF into the nucleus, which reduced cell death, whereas miR-210 inhibitors reversed this process, leading to cell death during hypoxia. Taken together, we report a novel feedback loop of BNIP3 regulation in NPCs under hypoxia. HIF-1 is activated under hypoxia and then induces the expression of both BNIP3 and miR-210. The upregulation of miR-210 then directly suppresses BNIP3 expression to maintain the survival of NPCs under hypoxia. This negative feedback regulation might partially contribute to protection against hypoxia-induced cell death via the inhibition of AIF nuclear translocation.
authors.affiliation: Department of Cognitive Sciences, Institute of Basic Medical Sciences, Beijing 100850, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Xiong
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.forename: Tong
authors.initials: T
authors.lastname: Zhao
authors.forename: Li-ying
authors.initials: LY
authors.lastname: Wu
authors.forename: Zhao-hui
authors.initials: ZH
authors.lastname: Liu
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Ding
authors.forename: Shuhong
authors.initials: S
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.forename: Yongqi
authors.initials: Y
authors.lastname: Zhao
authors.forename: Kuiwu
authors.initials: K
authors.lastname: Wu
authors.forename: Ling-ling
authors.initials: LL
authors.lastname: Zhu
authors.forename: Ming
authors.initials: M
authors.lastname: Fan
mesh_terms: D017209:Apoptosis / Q000502:physiology; D015687:Cell Hypoxia / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: C090121:BNIP3 protein, human; D051793:Hypoxia-Inducible Factor 1; C543800:MIRN210 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins