N‑Myc downstream‑regulated gene 2 restrains glycolysis and glutaminolysis in clear cell renal cell carcinoma

Shi,Wei; Xu,Xinyuan; Yan,Fei; Wang,Bao; Zhao,Hang; Chan,Aaron; Ren,Zhen; Ma,Yongzheng; Wang,Fuli; Yuan,Jianlin

doi:10.3892/ol.2017.7024

N‑Myc downstream‑regulated gene 2 restrains glycolysis and glutaminolysis in clear cell renal cell carcinoma

Authors:
- Wei Shi
- Xinyuan Xu
- Fei Yan
- Bao Wang
- Hang Zhao
- Aaron Chan
- Zhen Ren
- Yongzheng Ma
- Fuli Wang
- Jianlin Yuan
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Affiliations: Department of Urology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China, Department of Biochemistry, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China, Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China, Department of Pharmacology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China, Department of Oncology, Internal Medicine, University of California, Davis, CA 95817, USA
Published online on: September 22, 2017 https://doi.org/10.3892/ol.2017.7024
Pages: 6881-6887

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Abstract

Glycolysis and glutaminolysis are heavily involved in the metabolic reprogramming of cancer cells. The activation of oncogenes and inactivation of tumor suppressor genes has a marked effect on the cellular metabolic processes glycolysis and glutaminolysis. N‑Myc downstream‑regulated gene 2 (NDRG2) is a tumor suppressor gene that previous studies have demonstrated can inhibit the growth, proliferation and metastasis of clear cell renal cell carcinoma (ccRCC) cells. However, the function of NDRG2 in ccRCC metabolism remains unknown. In the present study, NDRG2 significantly inhibited the consumption of glucose and glutamine, as well as the production of lactate and glutamate in ccRCC. NDRG2 significantly suppressed the expression of glucose transporter 1, hexokinase 2, pyruvate kinase M2, lactate dehydrogenase A, glutamine transporter ASC amino acid transporter 2 and glutaminase 1 at the mRNA (by quantitative polymerase chain reaction) and protein level (by western blot analysis), all of which are key regulators and enzymes in glycolysis and glutaminolysis. Data from the present study also revealed that overexpression of NDRG2 suppressed cell proliferation in ccRCC in vitro and in vivo, demonstrated by colony formation assays, wound healing assay and nude mouse transplantation tumor experiment. The present findings demonstrate for the first time that NDRG2 acts as a key inhibitor of glycolysis and glutaminolysis in ccRCC and could be a promising target for the metabolic treatment of ccRCC.

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