HIF-1α up-regulates NDRG1 expression through binding to NDRG1 promoter, leading to proliferation of lung cancer A549 cells

Hypoxia-inducible signaling pathway is involved in many pathological processes, such as adaptiveness regulation of plateau environment, myocardial ischemia and tumorigenesis. NDRG1 is a member of the N-myc downregulated gene (NDRG) family, and it has strong hypoxia stress reaction functions. Althoug...

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Bibliographic Details
Published in:Molecular biology reports 2013-05, Vol.40 (5), p.3723-3729
Main Authors: Wang, Qiang, Li, Li-Hong, Gao, Guo-Dong, Wang, Gang, Qu, Liang, Li, Jin-Ge, Wang, Chun-Mei
Format: Article
Language:English
Subjects:
Animal Anatomy
Animal Biochemistry
Apoptosis - genetics
Biomedical and Life Sciences
Cell Cycle Proteins - genetics
Cell Hypoxia
Cell Line, Tumor
Cell Proliferation
Gene Expression
Gene Expression Regulation, Neoplastic
Histology
Humans
Hypoxia-Inducible Factor 1, alpha Subunit - genetics
Hypoxia-Inducible Factor 1, alpha Subunit - metabolism
Intracellular Signaling Peptides and Proteins - genetics
Life Sciences
Lung Neoplasms - genetics
Lung Neoplasms - metabolism
Morphology
Promoter Regions, Genetic
Protein Binding
Transcriptional Activation
Up-Regulation
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Summary:Hypoxia-inducible signaling pathway is involved in many pathological processes, such as adaptiveness regulation of plateau environment, myocardial ischemia and tumorigenesis. NDRG1 is a member of the N-myc downregulated gene (NDRG) family, and it has strong hypoxia stress reaction functions. Although the cellular responses to hypoxia are well known, little is known about the interaction between hypoxia-inducible transcription factor (HIF)-1α and NDRG1. In this study, we cloned HIF-1α CDS, NDRG1 promoter and its truncatures, constructed pCDNA3.0-Hif-1α and pGL3-basic-NDRG1. Reporter assay results showed that HIF-1α could bind to NDRG1 promoter to activate NDRG1 expression. Further results revealed that −1202 to −450 of NDRG1 promoter is the most important region for HIF-1α binding. Then, we constructed NDRG1 stable transfection cell line. Results from MTT, colony-forming assay and flow cytometry showed that NDRG1 overexpression results in more proliferation and less apoptosis of A549 lung cancer cells. Our study elucidates the mechanism of NGRG1 in hypoxia stress reactions and may provide new strategy for hypoxia injuries.
ISSN:0301-4851
1573-4978
DOI:10.1007/s11033-012-2448-4