NDRG2 is a new HIF-1 target gene necessary for hypoxia-induced apoptosis in A549 cells

Lifeng Wang, Na Liu, Libo Yao, Fuyang Li, Jiang Zhang, Yanchun Deng, Junye Liu, Shaoping Ji, Angang Yang, Hua Han, Yingqi Zhang, Jing Zhang, Wei Han, Xinping Liu

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

The NDRG2 gene belongs to a family of N-Myc downstream-regulated genes (NDRGs) and is expressed in many normal tissues. NDRG2 gene expression has been shown to be regulated in the stress response of certain cells. However, its function is not yet fully understood. Many studies have demonstrated that hypoxia, one of the stress responses, induced apoptosis in several cell types. In the current study, we investigated NDRG2 involvement in hypoxia response and found that NDRG2 expression was markedly up-regulated in several tumor cell lines exposed to hypoxic conditions or similar stresses at the mRNA and protein level. We also observed that the expression of NDRG2 was regulated by Hypoxia-inducible factor 1 (HIF-1) in tumor cells under hypoxia. Three hypoxia-responsive elements (HREs) in the NDRG2 promoter were identified. HRE1 could directly bind Hif-1 in vivo. Importantly, we found that silencing or enforcing the expression of NDRG2 could strongly inhibit or increase apoptosis. In addition, our data also showed that Ndrg2 was able to be translocated from the cytoplasm to the nucleus, and the segment from 101 to 178 amino acids of Ndrg2 is responsible for its translocation. Taken together, this study suggests that NDRG2 is a Hif-1 target gene and closely related with hypoxia-induced apoptosis in A549 cells.

Original languageEnglish (US)
Pages (from-to)239-250
Number of pages12
JournalCellular Physiology and Biochemistry
Volume21
Issue number1-3
DOIs
StatePublished - 2008

Keywords

  • Apoptosis
  • HIF-1
  • Hypoxia
  • NDRG2 gene

ASJC Scopus subject areas

  • Physiology

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