基础医学与临床 ›› 2025, Vol. 45 ›› Issue (5): 622-626.doi: 10.16352/j.issn.1001-6325.2025.05.0622

• 研究论文 • 上一篇    下一篇

GOT2调控急性髓系白血病细胞的天冬氨酸含量和存活

刘译阳, 王芳, 余佳, 李卫倩*   

  1. 中国医学科学院基础医学研究所 北京协和医学院基础学院 医学分子生物学国家重点实验室,北京 100005
  • 收稿日期:2025-02-13 修回日期:2025-03-18 出版日期:2025-05-05 发布日期:2025-04-23
  • 通讯作者: * liweiqiano@163.com
  • 基金资助:
    国家自然科学青年科学基金(82300140)

GOT2 regulates aspartate levels and viability in acute myeloid leukemia cells

LIU Yiyang, WANG Fang, YU Jia, LI Weiqian*   

  1. State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences CAMS, School of Basic Medicine PUMC, Bejing 100005, China
  • Received:2025-02-13 Revised:2025-03-18 Online:2025-05-05 Published:2025-04-23
  • Contact: * liweiqiano@163.com

摘要: 目的 探讨谷氨酸-草酰乙酸转氨酶2基因(GOT2)在急性髓系白血病细胞中的功能。方法 构建针对GOT2的shRNA,使用shRNA在人单核细胞白血病细胞系THP-1中抑制GOT2基因的表达。通过RT-qPCR检测GOT2 mRNA表达水平,Western blot检测GOT2蛋白表达水平的变化。采用比色法检测细胞内游离氨基酸含量变化。检测细胞GOT2表达缺失对THP-1细胞功能的影响,包括:CCK8法评估细胞增殖情况;流式细胞测量术分析细胞凋亡水平。结果 使用GOT2 shRNA干扰后,THP-1细胞GOT2的mRNA及蛋白表达水平均显著降低(P<0.05)。与对照组相比,敲低GOT2不影响细胞内谷氨酸含量(P>0.05),但会显著下调天冬氨酸含量(P<0.05);敲低GOT2显著降低了THP-1细胞的活性,使细胞增殖受阻(P<0.05)、凋亡增加(P<0.05)。结论 下调GOT2可显著降低急性髓系白血病细胞系内天冬氨酸水平,抑制细胞生长并诱导细胞凋亡,提示GOT2在急性髓系白血病的氨基酸代谢调控中可能发挥关键作用。

关键词: GOT2, 急性髓系白血病, 天冬氨酸

Abstract: Objective To investigate the function of the glutamic-oxaloacetic transaminase 2(GOT2) gene in acute myeloid leukemia cells. Methods ShRNAs targeting at GOT2 were constructed to suppress GOT2 expression in the THP-1 human monocytic leukemia cell line. GOT2 mRNA level was measured by RT-qPCR, and GOT2 protein expression was measured by Western blot. Intracellular free amino acid level was quantified using colorimetric assays. The impact of GOT2 knockdown in THP-1 cell function was evaluated through cell viability (CCK-8 assay) and apoptosis (flow cytometry). Results After GOT2 knockdown, both GOT2 mRNA and protein were significantly decreased in THP-1 cells(P<0.05). Compared to the control group, GOT2 knockdown did not affect intracellular glutamate levels(P>0.05), but led to a marked decrease in aspartate level(P<0.05). GOT2 knockdown significantly impaired THP-1 cell viability, inhibited cell proliferation(P<0.05) and promoted apoptosis(P<0.05). Conclusions Down regulation of GOT2 significantly decreases intracellular aspartate level in acute myeloid leukemia cells, impairs cellular viability and induces apoptosis, which suggests that GOT2 may play a key role in the regulation of amino acid metabolism in acute myeloid leukemia.

Key words: GOT2, acute myeloid leukemia, aspartate

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