Volume 20 Issue 1
Jan.  2022
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GENG Xi-lin, ZHANG Ying, LI Hao, ZHANG Yu, CHANG Hu-lin. Regulation of mitochondrial dynamic-related protein 1 on glucose metabolism in liver cancer cells[J]. Chinese Journal of General Practice, 2022, 20(1): 35-38. doi: 10.16766/j.cnki.issn.1674-4152.002270
Citation: GENG Xi-lin, ZHANG Ying, LI Hao, ZHANG Yu, CHANG Hu-lin. Regulation of mitochondrial dynamic-related protein 1 on glucose metabolism in liver cancer cells[J]. Chinese Journal of General Practice, 2022, 20(1): 35-38. doi: 10.16766/j.cnki.issn.1674-4152.002270

Regulation of mitochondrial dynamic-related protein 1 on glucose metabolism in liver cancer cells

doi: 10.16766/j.cnki.issn.1674-4152.002270
Funds:

 2020JQ-948

  • Received Date: 2020-05-18
    Available Online: 2022-03-03
  •   Objective  To explore the effect of mitochondrial dynamic-related protein 1 (DRP1) on glucose metabolism reprogramming in liver cancer cells.  Methods  After DRP1 was knocked down by siRNA in liver cancer SNU-739 cells, (1) To explore the effect of DRP1 on glycolysis of liver cancer, glucose uptake and lactate production were determined. (2) To explore the effect of DRP1 on oxidative phosphorylation of liver cancer, the oxygen consumption rate and ATP production were determined. (3) The effects of DRP1 knockdown on the levels of metabolites in glycolysis and the TCA cycle were determined by mass spectrometry analysis.  Results  (1) Down regulation of DRP1significantly inhibited glucose uptake and lactate production in SNU-739 cells (siCtrl: si-DRP1#1: si-DRP1#2=1.000±0.069:0, 417±0.032: 0.400±0.040: F=141.400, P < 0.001) and lactate production (siCtrl: si-DRP1#1: si-DRP1#2= 1.00±0.050:0.327±0.040: 0.310±0.036; F=256.700, P < 0.001). (2) Down regulation of DRP1 markedly increased the rate of oxygen consumption (siCtrl: si-DRP1#1: si-DRP1#2=1.000±0.069: 1.623±0.081: 1.591±0.046; F=81.720, P < 0.001) and ATP production (siCtrl: si-DRP1#1: si-DRP1#2= 1.000±0.062: 1.813±0.093:1.850±0.070; F=119.200, P < 0.001). (3) Down regulation of DRP1 decreased the levels of glucose, pyruvate and lactate (all P < 0.001) in glycolysis metabolism, but increased the levels of citrate, fumarate and malate (all P < 0.001) metabolites in the TCA cycle.  Conclusion  DRP1 reprogrammed glucose metabolism of liver cancer cells through increasing glycolysis and decreasing oxidative phosphorylation.

     

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  • [1]
    LUENGO A, GUI D Y, VANDER H M G, et al. Targeting metabolism for cancer therapy[J]. Cell Chem Biol, 2017, 24(9): 1161-1180. doi: 10.1016/j.chembiol.2017.08.028
    [2]
    LIN X H, QIU B Q, MA M, et al. Suppressing DRP1-mediated mitochondrial fission and mitophagy increases mitochondrial apoptosis of hepatocellular carcinoma cells in the setting of hypoxia[J]. Oncogenesis, 2020, 9(7): 67-82. doi: 10.1038/s41389-020-00251-5
    [3]
    MA M, LIN X H, LIU H H, et al. Suppression of DRP1-mediated mitophagy increases the apoptosis of hepatocellular carcinoma cells in the setting of chemotherapy[J]. Oncol Rep, 2020, 43(3): 1010-1018.
    [4]
    ABDEL-WAHAB A F, MAHMOUD W, AL-HARIZY R M, et al. Targeting glucose metabolism to suppress cancer progression: Prospective of anti-glycolytic cancer therapy[J]. Pharmacol Res, 2019, 150(2): 104-115.
    [5]
    MORRIS A. Inhibiting glycolysis in tumour cells[J]. Nat Rev Endocrinol, 2018, 14(6): 323-346.
    [6]
    LEBELO M T, JOUBERT A M, VISAGIE M H, et al. Warburg effect and its role in tumourigenesis[J]. Arch Pharm Res, 2019, 42(10): 833-847. doi: 10.1007/s12272-019-01185-2
    [7]
    ABBASZADEH Z, ÇEŞMELI S, BIRAY A Ç. Crucial players in glycolysis: Cancer progress[J]. Gene, 2020, 726(1): 144-158.
    [8]
    GANAPATHY-KANNIAPPAN S. Molecular intricacies of aerobic glycolysis in cancer: Current insights into the classic metabolic phenotype[J]. Crit Rev Biochem Mol Biol, 2018, 53(6): 667-682. doi: 10.1080/10409238.2018.1556578
    [9]
    XIE Y, SHI X, SHENG K, et al. PI3K/Akt signaling transduction pathway, erythropoiesis and glycolysis in hypoxia (Review)[J]. Mol Med Rep, 2019, 19(2): 783-791.
    [10]
    IMOTO Y, ITOH K, FUJIKI Y, et al. Molecular basis of mitochondrial and peroxisomal division machineries[J]. Int J Mol Sci, 2020, 21(15): 545-552.
    [11]
    KIM Y Y, YUN S H, YUN J, et al. Downregulation of drp1, a fission regulator, is associated with human lung and colon cancers[J]. Acta Biochim Biophys Sin (Shanghai), 2018, 50(2): 209-215. doi: 10.1093/abbs/gmx137
    [12]
    KITAMURA S, YANAGI T, IMAFUKU K, et al. Drp1 regulates mitochondrial morphology and cell proliferation in cutaneous squamous cell carcinoma[J]. J Dermatol Sci, 2017, 88(3): 298-307. doi: 10.1016/j.jdermsci.2017.08.004
    [13]
    LIMA A R, SANTOS L, CORREIA M, et al. Dynamin-related protein 1 at the crossroads of cancer[J]. Genes(Basel), 2018, 9(2): 115-124.
    [14]
    NAGDAS S, KASHATUS J A, NASCIMENTO A, et al. Drp1 promotes Kras-driven metabolic changes to drive pancreatic tumor growth[J]. Cell Rep, 2019, 28(7): 1845-1859. doi: 10.1016/j.celrep.2019.07.031
    [15]
    YIN M, LU Q, LIU X, et al. Silencing Drp1 inhibits glioma cells proliferation and invasion by RHOA/ ROCK1 pathway[J]. Biochem Biophys Res Commun, 2016, 478(2): 663-668. doi: 10.1016/j.bbrc.2016.08.003
    [16]
    LIANG J, YANG Y, BAI L, et al. DRP1 upregulation promotes pancreatic cancer growth and metastasis through increased aerobic glycolysis[J]. J Gastroenterol Hepatol, 2019, 35(5): 885-895. doi: 10.1111/jgh.14912
    [17]
    SALAZAR C, ELORZA A A, COFRE G, et al. The OXPHOS supercomplex assembly factor HIG2A responds to changes in energetic metabolism and cell cycle[J]. J Cell Physiol, 2019, 234(10): 17405-17419. doi: 10.1002/jcp.28362
    [18]
    LI J, HUANG Q, LONG X, et al. Mitochondrial elongation-mediated glucose metabolism reprogramming is essential for tumour cell survival during energy stress[J]. Oncogene, 2017, 36(34): 4901-4912. doi: 10.1038/onc.2017.98
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