Document Detail

DNA demethylation regulates the expression of miR-210 in neural progenitor cells subjected to hypoxia.
MedLine Citation:
PMID:  23039253     Owner:  NLM     Status:  MEDLINE    
Several studies have identified a set of hypoxia-regulated microRNAs, among which is miR-210, whose expression is highly induced by hypoxia in various cancer cell lines. Recent studies have highlighted the importance of miR-210 and its transcriptional regulation by the transcription factor hypoxia-inducible factor-1 (HIF-1). We report here that the expression of miR-210 was highly induced in neural progenitor cells (NPCs) subjected to hypoxia. Specifically, treating hypoxic NPCs with the DNA demethylating agent 5-aza-2'-deoxycytidine significantly increased the expression of miR-210, even under normoxia; however, the activity of hypoxia-inducible factor-1 was unaffected. Further analysis of the miR-210 sequence revealed that it is embedded in a CpG island. Bisulfite sequencing of the miR-210 CpG island from NPCs grown under hypoxic conditions showed 24% CpG methylation in NPCs exposed to 20% O(2) , 18% in NPCs exposed to 3% O(2) , and 12% in NPCs exposed to 0.3% O(2) . In addition, the activity of DNA methyltransferases (DNMTs) in NPCs decreased after exposure to hypoxia. Specifically, the expression of DNMT3b decreased significantly after exposure to 0.3% O(2) . Thus, these results demonstrate that DNA demethylation regulates miR-210 expression in NPCs under both normoxia and hypoxia.
Lei Xiong; Fei Wang; Xin Huang; Zhao-hui Liu; Tong Zhao; Li-ying Wu; Kuiwu Wu; Xuefeng Ding; Shuhong Liu; Yan Wu; Yongqi Zhao; Ling-ling Zhu; Ming Fan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-11-07
Journal Detail:
Title:  The FEBS journal     Volume:  279     ISSN:  1742-4658     ISO Abbreviation:  FEBS J.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-22     Completed Date:  2013-01-25     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  101229646     Medline TA:  FEBS J     Country:  England    
Other Details:
Languages:  eng     Pagination:  4318-26     Citation Subset:  IM    
Copyright Information:
© 2012 The Authors Journal compilation © 2012 FEBS.
Department of Cognitive Sciences, Institute of Basic Medical Sciences, Beijing, China; College of Life Science, Wuhan University, Wuhan, China.
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MeSH Terms
Azacitidine / analogs & derivatives,  pharmacology
Blotting, Western
Cell Hypoxia / genetics,  physiology*
Cells, Cultured
DNA Methylation / drug effects,  genetics,  physiology*
DNA Modification Methylases / genetics,  metabolism
Hypoxia-Inducible Factor 1 / genetics,  metabolism
MicroRNAs / genetics,  metabolism*
Neural Stem Cells / metabolism*
Polymerase Chain Reaction
Rats, Wistar
Reg. No./Substance:
0/Hypoxia-Inducible Factor 1; 0/MIRN210 microRNA, rat; 0/MicroRNAs; 320-67-2/Azacitidine; 776B62CQ27/decitabine; EC 2.1.1.-/DNA Modification Methylases

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