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

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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.

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Acknowledgments

This work was supported by Grants from the National Natural Science Foundation of China (3097243).

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Authors and Affiliations

  1. Center for Electronic Microscope, Fourth Military Medical University, **’an, 710032, China

    Qiang Wang & Chun-Mei Wang

  2. Institute of Digestive Diseases, ****g Hospital, State Key Laboratory of Cancer Biology, The Fourth Military Medical University, **’an, 710032, China

    **-Ge Li

  3. Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, **’an, 710038, China

    Qiang Wang, Li-Hong Li, Guo-Dong Gao, Liang Qu & Chun-Mei Wang

  4. Department of Renal Department of Internal Medicine, ****g Hospital, The Fourth Military Medical University, **’an, 710032, China

    Gang Wang

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  1. Qiang Wang
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  4. Gang Wang
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Correspondence to **-Ge Li or Chun-Mei Wang.

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Qiang Wang and Li-Hong Li contributed equally to this work.

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Wang, Q., Li, LH., Gao, GD. et al. HIF-1α up-regulates NDRG1 expression through binding to NDRG1 promoter, leading to proliferation of lung cancer A549 cells. Mol Biol Rep 40, 3723–3729 (2013). https://doi.org/10.1007/s11033-012-2448-4

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  • DOI: https://doi.org/10.1007/s11033-012-2448-4

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