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Expression of oxidored nitro domain-containing protein 1(NOR1) impairs nasopharyngeal carcinoma cells adaptation to hypoxia and inhibits PDK1 expression

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Abstract

Hypoxia is a characteristic pathophysiological property of locally advanced solid tumors and a relevant factor of the tumor (patho-)physiome since it can promote tumor progression and resistance to therapy. Tumors alter their metabolic pathways to survive in nutrient and oxygen poor microenvironments by a process known as the “Warburg Effect.” The current studies identify a novel tumor suppressor gene, termed oxidored nitro domain-containing protein 1 (NOR1) which alters hypoxia cellular response in nasopharyngeal carcinoma. NOR1 expression causes apoptosis of tumor cells in hypoxia by altering the expression of PDK1 expression and mitochondrial Bax-Bcl2 balance thus suppress tumor cell adaptation to hypoxia. Although the importance of hypoxia cellular response is well documented in tumor progression, this is the first demonstration of a human tumor suppressor which functions by regulating mitochondrial apoptotic pathways to suppress tumor survival in oxygen poor microenvironments.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (81000883, 81372304, 81272254, 81171930 and 81102065), the Natural Science Foundation of Hunan Province, China (14JJ3045), the National “111” Project (111-2-12), Specialized Research Fund for the Doctoral Program of Higher Education (20110162120009).

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Authors and Affiliations

  1. Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, China

    Bo Xiang, Wenjuan Li, Wei Wang, Pan Zheng, Xiaoling Li & Guiyuan Li

  2. Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Xiangya Road, Changsha, 410078, Hunan, China

    Bo Xiang, Wenjuan Li, Wei Wang, Pan Zheng, Xiaoling Li & Guiyuan Li

  3. Department of Dermatology, Xiangya Hospital of Central South University, Changsha, 410008, China

    Mei Yi

  4. Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, 410013, China

    Mei Yi

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  1. Bo Xiang
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  2. Mei Yi
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  3. Wenjuan Li
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  4. Wei Wang
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  6. Xiaoling Li
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  7. Guiyuan Li
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Corresponding author

Correspondence to Guiyuan Li.

Electronic supplementary material

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11010_2014_2072_MOESM1_ESM.tif

Supplementary Figure 1 PDK1 mRNA level in hypoxia condition. Realtime quantitative RT-PCR assay of PDK1 mRNA level in normoxia and CoCl2 (150 µM) treatment. PDK1 mRNA in IRES vector-transfected 5-8F cells (white) was significantly induced by CoCl2, however, it’s not so obvious in NOR1 re-expressing cells (black). (TIFF 1520 kb)

Supplementary material 2 (DOC 26 kb)

Supplementary material 3 (DOC 665 kb)

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Xiang, B., Yi, M., Li, W. et al. Expression of oxidored nitro domain-containing protein 1(NOR1) impairs nasopharyngeal carcinoma cells adaptation to hypoxia and inhibits PDK1 expression. Mol Cell Biochem 393, 293–300 (2014). https://doi.org/10.1007/s11010-014-2072-9

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  • DOI: https://doi.org/10.1007/s11010-014-2072-9

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