title: HIF-1α up-regulates NDRG1 expression through binding to NDRG1 promoter, leading to proliferation of lung cancer A549 cells.
abstract: 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.
authors.affiliation: Center for Electronic Microscope, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Li
authors.forename: Guo-Dong
authors.initials: GD
authors.lastname: Gao
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.forename: Liang
authors.initials: L
authors.lastname: Qu
authors.forename: Jin-Ge
authors.initials: JG
authors.lastname: Li
authors.forename: Chun-Mei
authors.initials: CM
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics*; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D015533:Transcriptional Activation; D015854:Up-Regulation; D000099259:N-myc Downstream-Regulated Gene 1 Protein
chemical_list: D018797:Cell Cycle Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D047908:Intracellular Signaling Peptides and Proteins; D000099259:N-myc Downstream-Regulated Gene 1 Protein