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: Fei Wang, Lei Xiong, Xin Huang, Tong Zhao, Li-ying Wu, Zhao-hui Liu, Xuefeng Ding, Shuhong Liu, Yan Wu, Yongqi Zhao, Kuiwu Wu, Ling-ling Zhu, Ming Fan
• Journal: Stem cell research (Stem Cell Res) Vol. 11 Issue 1 Pg. 657-67 (Jul 2013) ISSN: 1876-7753 [Electronic] England
• PMID: 23688833 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• BNIP3 protein, human
• Hypoxia-Inducible Factor 1
• MIRN210 microRNA, human
• Membrane Proteins
• MicroRNAs
• Proto-Oncogene Proteins

Topics

• Apoptosis (physiology)
• Cell Hypoxia (genetics, physiology)
• Cells, Cultured
• Humans
• Hypoxia-Inducible Factor 1 (biosynthesis, genetics, metabolism)
• Membrane Proteins (antagonists & inhibitors, genetics, metabolism)
• MicroRNAs (antagonists & inhibitors, biosynthesis, metabolism)
• Neural Stem Cells (cytology, metabolism)
• Proto-Oncogene Proteins (antagonists & inhibitors, genetics, metabolism)
• Transcriptional Activation