丝氨酸代谢对肾癌细胞增殖和迁移能力的影响

Effect of serine metabolism on the proliferation and migration of renal cancer cells

目的明确丝氨酸代谢对肾癌细胞增殖和迁移能力的影响,探索丝氨酸羟甲基转移酶1(SHMT1)在肾癌中表达水平和肾癌患者预后的关系。方法通过对肾癌细胞给予丝氨酸过量处理,利用CCK8实验检测丝氨酸对肾癌细胞增殖能力的影响,细胞周期实验检测对细胞周期进程的影响,划痕实验检测对迁移能力的影响。通过TCGA数据库分析SHMT1在肾癌组织中表达水平及其与肾癌患者生存率的关系,并且利用WebGestalt在线分析工具对靶基因进行GO分析和KEGG信号通路富集。结果给予肾癌细胞丝氨酸过量处理可促进肾癌细胞的增殖能力,并且增强769-P及Caki-1细胞的迁移能力。给予肾癌细胞丝氨酸过量处理后,加速了肾癌细胞向G0/G1期的转换。通过TCGA数据库分析发现SHMT1在肾癌组织低表达,且病理分期越高,表达水平越低,并且SHMT1与肾癌患者临床不良预后相关。KEGG富集分析发现SHMT1主要参与调控mTOR信号传导途径、Ras信号传导途径及钙信号传导等途径。结论丝氨酸过量处理可促进肾癌细胞的增殖能力和迁移能力,控制患者饮食中丝氨酸摄入量可能成为改善肾癌患者进展的一种新的重要策略。SHMT1在肾癌组织低表达且与肾癌患者临床不良预后相关,提示SHMT1可作为评价肾癌患者预后的一种新的生物标记物。

Objective To determine the effect of serine metabolism on the proliferation and migration ability of kidney cancer cells,and to explore the relationship between the expression level of serine hydroxymethyltransferase 1(SHMT1)in kidney cancer and the prognosis of kidney cancer patients.Methods The effect of serine on the proliferation ability of kidney cancer cells was examined by administering serine 30 mg/L treatment to kidney cancer cells using the CCK8 assay.The effect of serine on the cell cycle progression of kidney cancer cells was examined by administering serine overdose treatment to kidney cancer cells using the cell cycle assay.The effect of serine on the migration ability of kidney cancer cells was examined by administering serine overdose treatment to kidney cancer cells using a scratch assay.The expression level of SHMT1 in kidney cancer tissues and its relationship with the survival rate of kidney cancer patients were analyzed by TCGA database,and the target genes were enriched for GO analysis and KEGG signaling pathway by using WebGestalt online analysis tool.Results Serine over-treatment of renal cancer cells promoted the proliferation ability of renal cancer cells and enhanced the migration ability of 769-P and Caki-1 cells.Administration of serine overtreatment to kidney cancer cells accelerated the conversion of kidney cancer cells to G0/G1 phase.KEGG enrichment analysis revealed that SHMT1 was mainly involved in the regulation of mTOR signaling pathway,Ras signaling pathway and calcium signaling pathway.Conclusion Serine overtreatment can promote the proliferation and migration of renal cell carcinoma cells,so controlling the dietary serine intake of patients may become a new important strategy to improve the progression of renal cell carcinoma.The low expression of SHMT1 in kidney cancer tissues and its association with poor clinical prognosis suggest that SHMT1 may be a new biomarker to evaluate the prognosis of kidney cancer patients.