title: NDRG2 is a new HIF-1 target gene necessary for hypoxia-induced apoptosis in A549 cells.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an, PR China.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Wang
authors.forename: Na
authors.initials: N
authors.lastname: Liu
authors.forename: Libo
authors.initials: L
authors.lastname: Yao
authors.forename: Fuyang
authors.initials: F
authors.lastname: Li
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhang
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Deng
authors.forename: Junye
authors.initials: J
authors.lastname: Liu
authors.forename: Shaoping
authors.initials: S
authors.lastname: Ji
authors.forename: Angang
authors.initials: A
authors.lastname: Yang
authors.forename: Hua
authors.initials: H
authors.lastname: Han
authors.forename: Yingqi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Han
authors.forename: Xinping
authors.initials: X
authors.lastname: Liu
mesh_terms: D017209:Apoptosis; D001665:Binding Sites; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D021381:Protein Transport; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
chemical_list: D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C466228:NDRG2 protein, human; D025521:Tumor Suppressor Proteins; D008156:Luciferases