LOX1在胃癌中的表达及其促肿瘤生长的机制探讨

目的:探讨血凝素样氧化型低密度脂蛋白受体1（lectin-like oxidized low density lipoprotein receptor-1，LOX1）在胃癌中的表达及与预后相关性，同时明确其促胃癌生长作用及潜在机制。方法:利用人类癌症基因组图谱(TCGA)、基因表达汇编(GEO)和癌症细胞系百科全书(CCLE)数据库分析LOX1在胃癌组织和细胞中的表达水平；利用多种统计方法分析LOX1表达水平与胃癌患者预后及临床特征的相关性；通过质粒转染敲低LOX1，进一步应用细胞功能实验（CCK-8、克隆形成、EdU实验）探究LOX1对胃癌细胞增殖能力的调控作用；通过Western blot、qPCR、免疫荧光分析LOX1对NF-κB信号通路激活的调控作用。结果:LOX1在胃癌组织和细胞中显著高表达；高水平LOX1提示胃癌患者预后较差且肿瘤较易发生转移；敲低LOX1显著抑制肿瘤细胞增殖；敲低LOX1显著抑制胃癌细胞中NF-κB信号通路的激活。结论:LOX1通过激活NF-κB信号通路对胃癌细胞增殖能力具有调控作用；LOX1可作为生物标记物提示患者预后；靶向LOX1可作为潜在胃癌治疗新方案。

Expression of LOX1 in gastric cancer and its mechanism of promoting tumor growth

Objective:To investigate the expression of lectin-like oxidized low density lipoprotein receptor-1 (LOX1) in gastric cancer (GC) and its correlation with prognosis.And, to reveal the mechanism of LOX1 promoting GC growth.Methods:The Cancer Genome Atlas (TCGA),Gene Expression Omnibus (GEO),and Cancer Cell Line Encyclopedia (CCLE) database were used to identify the expression of LOX1 in GC tissues and cells.The correlation between LOX1 expression levels and prognosis,clinical features in GC patients was analyzed by various statistical methods.After plasmid transfection to knock down LOX1 expression,further cell function experiments (CCK-8,clone formation,EdU experiments) were conducted to investigate the regulatory effect of LOX1 on the proliferation ability of GC cells.Western blot,qPCR and immunofluorescence assays were performed to evaluate the regulatory role of LOX1 on NF-κB signaling pathway activation.Results:LOX1 expression was significantly upregulated in GC tissues and cells.Higher expression of LOX1 indicated poor prognosis and tumor metastasis in GC patients.LOX1 knockdown significantly inhibited tumor cell proliferation.In addition,LOX1 knockdown significantly restrained the activation of NF-κB signaling pathway in GC cells.Conclusion:LOX1 has a regulatory effect on GC cell proliferation by activating NF-κB signaling pathway.LOX1 is a promising biomarker for diagnosis and prognosis of GC patients and targeting LOX1 may be a new diagnostic and therapeutic strategy for GC.