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  • DNA demethylation regulates the expression of miR-210 in neural progenitor cells subjected to hypoxia.

DNA demethylation regulates the expression of miR-210 in neural progenitor cells subjected to hypoxia.

The FEBS journal (2012-10-09)
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
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.

MATERIALS
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Product Description

Sigma-Aldrich
Monoclonal Anti-HIF-1α antibody produced in mouse, ~1 mg/mL, clone H1α67, purified immunoglobulin, buffered aqueous solution