title: DNA demethylation regulates the expression of miR-210 in neural progenitor cells subjected to hypoxia.
abstract: 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.
authors.affiliation: Department of Cognitive Sciences, Institute of Basic Medical Sciences, Beijing, China;  College of Life Science, Wuhan University, Wuhan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Xiong
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.forename: Zhao-hui
authors.initials: ZH
authors.lastname: Liu
authors.forename: Tong
authors.initials: T
authors.lastname: Zhao
authors.forename: Li-ying
authors.initials: LY
authors.lastname: Wu
authors.forename: Kuiwu
authors.initials: K
authors.lastname: Wu
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: Ling-ling
authors.initials: LL
authors.lastname: Zhu
authors.forename: Ming
authors.initials: M
authors.lastname: Fan
mesh_terms: D000818:Animals; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D015153:Blotting, Western; D015687:Cell Hypoxia / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D015254:DNA Modification Methylases / Q000235:genetics / Q000378:metabolism; D000077209:Decitabine; D005260:Female; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D058953:Neural Stem Cells / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
chemical_list: D051793:Hypoxia-Inducible Factor 1; C546388:MIRN210 microRNA, rat; D035683:MicroRNAs; D000077209:Decitabine; D015254:DNA Modification Methylases; D001374:Azacitidine