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Widely targeted metabolomic analyses unveil the metabolic variations after stable knock-down of NME4 in esophageal squamous cell carcinoma cells

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Abstract

NME4, also designated nm23-H4 or NDPK-D, has been known for years for its well-established roles in the synthesis of nucleoside triphosphates, though; little has been known regarding the differential metabolites involved as well as the biological roles NME4 plays in proliferation and invasion of esophageal squamous cell carcinoma (ESCC) cells. To understand the biological roles of NME4 in ESCC cells, lentiviral-based short hairpin RNA interference (shRNA) vectors were constructed and used to stably knock down NME4. Then, the proliferative and invasive variations were assessed using MTT, Colony formation and Transwell assays. To understand the metabolites involved after silencing of NME4 in ESCC cells, widely targeted metabolomic screening was taken. It was discovered that silencing of NME4 can profoundly suppress the proliferation and invasion in ESCC cells in vitro. Metabolically, a total of 11 differential metabolites were screened. KEGG analyses revealed that Tryptophan, Riboflavin, Purine, Nicotinate, lysine degradation, and Linoleic acid metabolism were also involved in addition to the well-established nucleotides metabolism. Some of these differential metabolites, say, 2-Picolinic Acid, Nicotinic Acid and Pipecolinic Acid were suggested to be associated with tumor immunomodulation. The data we described here support the idea that metabolisms occurred in mitochondrial was closely related to tumor immunity.

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Acknowledgements

The study was partly supported by Nature Science Foundation of China (NSFC.81960552, 81960527, 81960527, U1603284, 81860511), and partly by Science and Technology Projects of Xinjiang Uygur Autonomous Region (2018E02067), by Tianshan Xuesong Project of the Xinjiang Uygur Autonomous Region (2018XS19).

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Authors and Affiliations

  1. Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Ürümqi, People’s Republic of China

    Shutao Zheng, Qing Liu, Lifei Yang, Qiqi Zhang, Xiujuan Han, Tongxue Shen, Xiao Zhang & Xiaomei Lu

  2. State Key Laboratory of Pathogenesis, Prevention, Treatment of Central Asian High Incidence Diseases, Xinjiang Uygur Autonomous Region, Ürümqi, People’s Republic of China

    Shutao Zheng, Qing Liu, Lifei Yang, Qiqi Zhang, Xiujuan Han, Tongxue Shen, Xiao Zhang & Xiaomei Lu

  3. Health Management Center, Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Ürümqi, People’s Republic of China

    Tao Liu

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  1. Shutao Zheng
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Zheng, S., Liu, T., Liu, Q. et al. Widely targeted metabolomic analyses unveil the metabolic variations after stable knock-down of NME4 in esophageal squamous cell carcinoma cells. Mol Cell Biochem 471, 81–89 (2020). https://doi.org/10.1007/s11010-020-03768-w

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