eEF1A1在结直肠癌转移中的作用及机制研究

Role and mechanism of eEF1A1 in metastasis of colorectal cancer

摘要

目的 探究真核翻译延伸因子1A1(eEF1A1)在结直肠癌(CRC)组织中的表达情况, 明确其对CRC细胞转移能力的调控作用, 并深入挖掘背后潜在分子机制。方法 借助公共数据库资源分析eEF1A1在CRC中的表达特征及其与临床病理参数的关联, 明确其临床意义; 通过分子生物学技术构建eEF1A1稳定敲减及过表达CRC细胞系; 体外采用Transwell实验检测eEF1A1对CRC细胞转移能力的影响; 体内通过建立裸鼠尾静脉肺转移模型, 观察并统计模型小鼠肺部肿瘤转移灶的形成情况及转移结节数量; 结合蛋白质蛋白质相互作用网络构建和功能富集分析探讨eEF1A1相互作用的分子以及可能机制。结果 TCGA数据库分析显示, eEF1A1在CRC组织高表达, 且eEF1A1高表达的CRC患者预后较差; GEO公共数据库分析显示, M1期的eEF1A1表达显著高于M0期; Transwell实验提示, 敲减eEF1A1显著抑制RKO细胞迁移和侵袭(P<0.01), 过表达eEF1A1促进HCT8细胞迁移和侵袭(P<0.01)。裸鼠尾静脉肺转移模型提示, eEF1A1过表达后, 肿瘤结节和转移灶明显增加, 敲减后减少。STRING数据库预测eEF1A1潜在的10个互作蛋白质分子主要为核糖体蛋白家族和翻译延伸因子组分; Reactome分析提示高度富集的翻译延伸/起始/信号识别颗粒(SRP)靶向通路可能在eEF1A1对CRC的转移过程中发挥重要作用。结论 eEF1A1在CRC中高表达, 并可能通过协调翻译延伸效率、起始调控及SRP通路促进CRC转移。该研究为未来靶向治疗提供了新的靶点及依据。

Abstract

Objective To investigate the expression of eukaryotic elongation factor 1 alpha 1 (eEF1A1) in colorectal cancer (CRC) tissues, clarify its regulatory role in CRC cell metastatic capacity, and deeply explore the underlying molecular mechanisms. Methods Public database resources were utilized to analyze eEF1A1 expression patterns in CRC and its association with clinicopathological parameters, clarifying its clinical significance. Molecular biology techniques were employed to establish stable eEF1A1 knockdown and overexpression CRC cell lines. In vitro Transwell assays were conducted to assess eEF1A1's impact on CRC cell metastatic capacity. In vivo, a nude mouse tail vein lung metastasis model was established to observe and quantify the formation of pulmonary metastatic lesions and the number of metastatic nodules in model mice. Protein interaction network construction and functional enrichment analysis were combined to explore molecules interacting with eEF1A1 and potential underlying mechanisms. Results The analysis of the TCGA database indicated that eEF1A1 was remarkedly upregulated in CRC tissues and CRC patients exhibiting high eEF1A1 expression had poorer prognosis. Analysis of the GEO public database revealed that eEF1A1 expression in M1 stage was significantly higher than that in M0 stage. Transwell assay indicated that eEF1A1 knockdown significantly inhibited RKO cell metastasis and invasion (P<0.01), while eEF1A1 overexpression promoted HCT8 cell metastasis and invasion (P<0.01). The model of pulmonary metastasis of tail vein in nude mice suggested that eEF1A1 overexpression led to significantly increased tumor nodules and metastases, with opposite effects observed after knockdown. The STRING database predicted 10 potential interacting proteins for eEF1A1, primarily comprising ribosomal proteins and translation elongation factors. Reactome analysis indicated that highly enriched translation elongation/initiation/SRP targeting pathways might play crucial roles in eEF1A1-mediated CRC metastasis. Conclusion eEF1A1 is highly expressed in CRC and may promote CRC metastasis by coordinating translation elongation efficiency, initiation regulation, and SRP pathways. This research provides new targets and basis for future targeted therapies.

关键词

结直肠癌 / 真核翻译延伸因子1A1 / GTP / 转移 / 侵袭 / 翻译调控 / 预后 / 机制

Key words

colorectal cancer / eukaryotic elongation factor 1 alpha 1 / GTP / metastasis / invasion / translational regulation / prognosis / mechanism

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基金资助

国家自然科学基金优秀青年科学基金(82222058)