LRFN4通过谷氨酰胺代谢途径影响胃癌细胞增殖

LRFN4 Regulates Gastric Cancer Cell Proliferation through Glutamine Metabolism

  • 摘要:
    背景 LRFN4是一种在癌症的发生和发展中起着关键作用的分子,在胃癌(gastric cancer,GC)中的作用以及与谷氨酰胺分解代谢的关系尚不清楚。目的 探讨LRFN4对胃癌的临床意义及预后预测价值,并通过体外细胞学实验分析验证其对胃癌细胞谷氨酰胺代谢的影响。方法 用生物信息学方法,借助TCGA、GEPIA和kmplot等数据库以及R语言软件,将数据分为LRFN4高表达组与LRFN4低表达组,以分析LRFN4对胃癌患者临床预后等方面的影响。使用体外胃癌细胞系HGC-27,构建差异表达LRFN4的胃癌细胞系,随后通过采用高效液相色谱-质谱联用测定差异表达LRFN4细胞系的谷氨酰胺摄取情况,用试剂盒检测谷氨酰胺酶活性及ATP与乳酸谷氨酰胺代谢通路的关键产物以评估差异表达LRFN4的谷氨酰胺代谢,采用CCK-8法检测差异表达LRFN4细胞系的增殖情况,利用流式细胞术检测差异表达LRFN4细胞系的凋亡,以验证LRFN4对胃癌细胞的生物学功能。结果 差异分析显示,LRFN4在胃癌组织中表达上调(P<0.05),预后分析表明,高表达组胃癌患者的总生存期和无病生存期均低于低表达组(P<0.05),提示LRFN4对胃癌患者的预后具有指导意义。LRFN4可能通过细胞周期等信号通路影响胃癌的发生发展。细胞实验证实LRFN4通过影响谷氨酰胺代谢促进细胞增殖(P<0.05)、抑制细胞凋亡(P<0.05)。结论 LRFN4可能通过影响谷氨酰胺代谢与胃癌患者的预后相关,在胃癌细胞中发挥癌基因的作用,促进肿瘤细胞增殖并抑制细胞凋亡。

     

    Abstract:
    Background LRFN4 is a pivotal molecule in the genesis and progression of cancer. Nevertheless, its function in Gastric Cancer (GC) and its correlation with glutamine catabolism remain elusive. Objective To explore the clinical significance and prognostic predictive value of LRFN4 in gastric cancer and to verify its impact on glutamine metabolism in gastric cancer cell lines through in-vitro cellular experiments. Methods Bioinformatics approaches were utilized to analyze the influence of LRFN4 on the clinical prognosis and other aspects of gastric cancer patients, by means of databases such as TCGA, GEPIA, and kmplot, along with R language software. Gastric cancer cell lines were employed to detect glutamine metabolic activity via glutamine uptake and glutaminase activity assays, CCK - 8 assay for cell proliferation, and flow cytometry for cell apoptosis, aiming to verify the biological functions of LRFN4 on gastric cancer cells. Results Differential analysis revealed that LRFN4 expression was markedly upregulated in gastric cancer tissues (P<0.05). Prognostic analysis indicated that both the overall survival and disease-free survival of gastric cancer patients in the high-expression group were lower than those in the low-expression group (P<0.05), suggesting that LRFN4 holds guiding significance for the prognosis of gastric cancer patients. LRFN4 may affect the occurrence and development of gastric cancer through signaling pathways like CELL CYCLE, promote cell proliferation (P<0.05), and inhibit cell apoptosis (P< 0.05) by influencing glutamine metabolism. Conclusion LRFN4 may be associated with the prognosis of gastric cancer patients by modulating glutamine metabolism, functioning as an oncogenic driver in gastric cancer cells, promoting tumor cell proliferation, and inhibiting cell apoptosis.

     

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