背景:透明细胞肾细胞癌(ccRCC)是一种具有高发病率和死亡率的世界性恶性肿瘤。翻译起始因子4A1(eIF4A1),它是一种ATP依赖性RNA解旋酶,作为eIF4F复合物的一部分,与恶性转化和进展有关,和各种癌症显示这种酶的失调。然而,其在ccRCC中的作用尚不清楚。在我们的研究中,我们研究了其在ccRCC中的潜在影响。
方法:基于蛋白质组数据,TCGA和ONCOMINE数据库,RCC细胞系和组织,研究了eIF4A1在ccRCC和正常组织之间的表达。评估OS的预后模型与ccRCC进展之间的相关性。进行了功能富集和PPI网络分析。在检查了eIF4A1高表达组和低表达组之间的差异表达基因后,我们进行了GSEA分析。此外,我们研究了eIF4A1的免疫细胞浸润。然后我们确定了eIF4A1在建立和维持细胞活力方面的功能,细胞系的迁移和侵袭。流式细胞术用于检测细胞周期。
结果:eIF4A1在ccRCC组织和细胞系中上调。eIF4A1水平的增加与较低的存活率和受损的免疫力有关。eIF4A1的耗尽可以将肿瘤细胞阻滞在G1期,从而严重限制细胞增殖,削弱细胞迁移能力。
结论:高表达eIF4A1的ccRCC患者预后不良的风险增加,此外,eIF4A1在促进肿瘤细胞增殖和迁移方面发挥着重要作用,这可能进一步成为潜在的预后生物标志物和治疗靶点.
BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a worldwide malignancy with high morbidity and mortality. Translation initiation factor 4A1 (
eIF4A1), which is an ATP-dependent RNA helicase as a part of eIF4F complex, has been linked to malignant transformation and progression, and a variety of cancers display dysregulation of this enzyme. However, its role in ccRCC remains unclear. In our study, we examined its potential effects in ccRCC.
METHODS: Based on Proteomic data, TCGA and ONCOMINE database, RCC cell lines and tissues, the expression of eIF4A1 between ccRCC and normal tissues were investigated. A correlation was evaluated between the prognostic model for OS and ccRCC progression. Analysis of functional enrichment and PPI network were performed. After examining differentially expressed genes between the
eIF4A1 high and low-expression groups, we performed GSEA analysis. Furthermore, we investigated immune cell infiltration of
eIF4A1. Then we determined eIF4A1 functions in the establishment and maintenance of cell viability, migration and invasion of cell lines. Flow cytometry was utilized to detect cell cycle.
RESULTS: The
eIF4A1 was up-regulated in ccRCC tissues and cell lines. An increased level of
eIF4A1 was linked to lower survival rates and impaired immunity. Depletion of eIF4A1 could arrest tumor cells in G1 phase, so as to seriously limit cell proliferation and weaken the capacity of cell migration.
CONCLUSIONS: ccRCC patients with high eIF4A1 expression are at increased risk of poor prognosis, furthermore eIF4A1 plays a prominent role in facilitating tumor cell proliferation and migration which may further be a potential prognostic biomarker and therapeutic target.