许杨, 刘黎, 王李杰, 杨旭辉, 霍苗. 尿苷胞苷激酶2调控肺腺癌发生发展的机制研究[J]. 解放军医学院学报, 2022, 43(8): 880-886. DOI: 10.3969/j.issn.2095-5227.2022.08.012
引用本文: 许杨, 刘黎, 王李杰, 杨旭辉, 霍苗. 尿苷胞苷激酶2调控肺腺癌发生发展的机制研究[J]. 解放军医学院学报, 2022, 43(8): 880-886. DOI: 10.3969/j.issn.2095-5227.2022.08.012
XU Yang, LIU Li, WANG Lijie, YANG Xuhui, HUO Miao. Mechanisms of UCK2 regulating growth of lung adenocarcinoma[J]. ACADEMIC JOURNAL OF CHINESE PLA MEDICAL SCHOOL, 2022, 43(8): 880-886. DOI: 10.3969/j.issn.2095-5227.2022.08.012
Citation: XU Yang, LIU Li, WANG Lijie, YANG Xuhui, HUO Miao. Mechanisms of UCK2 regulating growth of lung adenocarcinoma[J]. ACADEMIC JOURNAL OF CHINESE PLA MEDICAL SCHOOL, 2022, 43(8): 880-886. DOI: 10.3969/j.issn.2095-5227.2022.08.012

尿苷胞苷激酶2调控肺腺癌发生发展的机制研究

Mechanisms of UCK2 regulating growth of lung adenocarcinoma

  • 摘要:
      背景  尿苷-胞苷激酶2(uridine-cytidine kinase 2,UCK2)在多种类型癌组织中过表达,其在肺腺癌(lung adenocarcinoma, LUAD)发生发展中的作用及其调控机制研究较少。
      目的  研究UCK2对LUAD发生发展的影响并探究其可能作用机制。
      方法  利用TCGA数据库中LUAD的RNA-seq数据,通过单因素独立预后分析筛选差异基因,与临床数据结合,筛选与LUAD分期和预后相关的基因。CCK-8和划痕试验验证UCK2对LUAD细胞的影响。通过GSEA分析UCK2对LUAD生长调控的可能分子机制,免疫印迹实验验证UCK2对LUAD细胞中mTOR通路的调控作用。糖摄取、乳酸和ATP测定验证UCK2通过mTOR通路对LUAD细胞糖酵解的影响。
      结果  对TCGA数据库的分析显示UCK2对LUAD患者预后具有较高预测价值。细胞实验结果显示,与对照组比较,过表达UCK2组A549和Calu3细胞增殖能力、迁移能力显著增加(P<0.001)。GSEA分析显示UCK2在LUAD中正向调控mTOR通路。进一步Western blot实验显示UCK2在A549细胞中可上调mTOR通路中的p-PI3K、p-AKT、p-mTOR蛋白的相对表达水平(P<0.001)。在A549细胞中,UCK2通过调控mTOR通路而促进糖摄取、乳酸和ATP。
      结论  UCK2基因通过激活mTOR通路促进LUAD生长和迁移。

     

    Abstract:
      Background  Uridine cytidine kinase 2 (UCK2) is overexpressed in multiple tumors, whereas there are few studies on the regulation mechanism of UCK2 in lung adenocarcinoma.
      Objective  To study the effect of UCK2 on growth of LUAD and explore its possible mechanism.
      Methods  Using the RNA-seq data of LUAD in TCGA database, we screened differential genes by univariate independent prognostic analysis. Combined with clinical data, the genes related to the stage and prognosis of lung adenocarcinoma were screened. The cell proliferation and migration ability were detected by CCK-8 and wound healing test. The mechanism of UCK2 on the growth regulation of lung adenocarcinoma was analyzed by GSEA. Western blot was performed to explore the regulatory effect of the target gene on mTOR pathway in lung adenocarcinoma cells. The effects of UCK2 on glycolysis of lung adenocarcinoma cells through mTOR pathway were measured by glucose uptake, lactic acid and ATP.
      Results  Among the lung adenocarcinoma patients in the TCGA database, UCK2 was positively correlated with the stage of lung adenocarcinoma and negatively correlated with clinical prognosis. Compared with the NC group, overexpression of UCK2 promoted the growth and migration of A549 and Calu3 cells (P<0.001). The high expression of UCK2 was positively correlated with the activation of mTOR pathway in LUAD identified by GSEA. Western blot analysis indicated that protein relative expression levels of p-PI3K, p-AKT, p-mTOR significantly increased by UCK2 in A549 cells (P<0.001). UCK2 increased glucose uptake, lactate and ATP in A549 cells by regulating mTOR pathway.
      Conclusion  UCK2 promotes the growth and migration of lung adenocarcinoma by activating mTOR pathway.

     

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