PMID- 23039253 OWN - NLM STAT- MEDLINE DCOM- 20130125 LR - 20220316 IS - 1742-4658 (Electronic) IS - 1742-464X (Linking) VI - 279 IP - 23 DP - 2012 Dec TI - DNA demethylation regulates the expression of miR-210 in neural progenitor cells subjected to hypoxia. PG - 4318-26 LID - 10.1111/febs.12021 [doi] AB - 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. CI - (c) 2012 The Authors Journal compilation (c) 2012 FEBS. FAU - Xiong, Lei AU - Xiong L AD - Department of Cognitive Sciences, Institute of Basic Medical Sciences, Beijing, China; College of Life Science, Wuhan University, Wuhan, China. FAU - Wang, Fei AU - Wang F FAU - Huang, Xin AU - Huang X FAU - Liu, Zhao-hui AU - Liu ZH FAU - Zhao, Tong AU - Zhao T FAU - Wu, Li-ying AU - Wu LY FAU - Wu, Kuiwu AU - Wu K FAU - Ding, Xuefeng AU - Ding X FAU - Liu, Shuhong AU - Liu S FAU - Wu, Yan AU - Wu Y FAU - Zhao, Yongqi AU - Zhao Y FAU - Zhu, Ling-ling AU - Zhu LL FAU - Fan, Ming AU - Fan M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20121107 PL - England TA - FEBS J JT - The FEBS journal JID - 101229646 RN - 0 (Hypoxia-Inducible Factor 1) RN - 0 (MIRN210 microRNA, rat) RN - 0 (MicroRNAs) RN - 776B62CQ27 (Decitabine) RN - EC 2.1.1.- (DNA Modification Methylases) RN - M801H13NRU (Azacitidine) SB - IM MH - Animals MH - Azacitidine/analogs & derivatives/pharmacology MH - Blotting, Western MH - Cell Hypoxia/genetics/*physiology MH - Cells, Cultured MH - DNA Methylation/drug effects/genetics/*physiology MH - DNA Modification Methylases/genetics/metabolism MH - Decitabine MH - Female MH - Hypoxia-Inducible Factor 1/genetics/metabolism MH - MicroRNAs/genetics/*metabolism MH - Neural Stem Cells/*metabolism MH - Polymerase Chain Reaction MH - Pregnancy MH - Rats MH - Rats, Wistar EDAT- 2012/10/09 06:00 MHDA- 2013/01/26 06:00 CRDT- 2012/10/09 06:00 PHST- 2012/06/29 00:00 [received] PHST- 2012/08/15 00:00 [revised] PHST- 2012/10/03 00:00 [accepted] PHST- 2012/10/09 06:00 [entrez] PHST- 2012/10/09 06:00 [pubmed] PHST- 2013/01/26 06:00 [medline] AID - 10.1111/febs.12021 [doi] PST - ppublish SO - FEBS J. 2012 Dec;279(23):4318-26. doi: 10.1111/febs.12021. Epub 2012 Nov 7.