研究动态
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Caprin-1通过调节METTL3和WTAP发挥细胞增殖和食管癌Warburg代谢的作用。

Caprin-1 plays a role in cell proliferation and Warburg metabolism of esophageal carcinoma by regulating METTL3 and WTAP.

发表日期:2023 Feb 28
作者: Yan Gao, Lingling Yuan, Changbin Ke, Zhijun Pei, Xiaobo Liu, Ruimin Wu, Xueyan Kui, Yanmin Zhang
来源: Journal of Translational Medicine

摘要:

胞浆激活/增殖相关蛋白-1(Caprin-1)参与了癌细胞增殖和肿瘤发生,但其在食管癌(ESCA)发展中的作用尚未研究。本研究使用生物学方法和数据分析研究了Caprin-1在ESCA组织和细胞系中的表达情况,全面分析了Caprin-1的mRNA表达和预后价值、ESCA信号通路,并利用公共数据库在线研究了CAPRIN1的生物学功能。通过颜色增殖检测、EdU染色、克隆形成、流式细胞术、凋亡分析、Western印迹、乳酸检测和细胞外酸化速率等方法,研究了CAPRIN1的作用机制。此外,构建异种移植瘤模型验证了Caprin-1沉默对表型的影响。结果显示,Caprin-1在ESCA肿瘤组织和细胞系中的表达显著升高,而在正常相邻组织和成纤维细胞中的表达较低。提高的CAPRIN1 mRNA表达与临床预后和诊断准确性密切相关。GO富集和KEGG途径分析表明,CAPRIN1可能与免疫相关术语、蛋白质结合过程和代谢途径有关。55个ESCA患者中,高Caprin-1蛋白水平与淋巴结转移(P=0.031)、ki-67(P=0.023)和18F−FDG PET/CT参数(SUVmax(P=0.002)和SUV平均值(P=0.005))呈显著正相关。在SUVmax 17.71和SUVmean 10.14的截断值下,18F−FDG PET/CT成像预测ESCA样品中的Caprin-1表达具有70.8%的敏感性和77.4%的特异性。体外和体内实验表明,Caprin-1敲下影响了ESCA瘤体生长。沉默Caprin-1抑制了ESCA细胞的增殖和糖酵解,并降低了转移酶类似物3(METTL3)和威廉姆斯肿瘤1结合蛋白(WTAP)的表达。但是,恢复METTL3和WTAP表达可部分逆转这种效应。我们的数据表明,Caprin-1可以作为一种预后生物标志物,并在ESCA中具有致癌作用。 ©2023年作者。
Cytoplasmic activation/proliferation-associated protein-1 (Caprin-1) is implicated in cancer cell proliferation and tumorigenesis; however, its role in the development of esophageal carcinoma (ESCA) has not been examined.Biological methods and data analysis were used to investigate the expression of Caprin-1 in ESCA tissue and cell lines. We comprehensively analyzed the mRNA expression and prognostic values, signalling pathways of CAPRIN1 in ESCA using public databases online. Biological functions of CAPRIN1 were performed by clorimetric growth assay, EdU staining, colony formation, flow cytometry, apoptosis analysis, Western blot, lactate detection assay, extracellular acidification rates. The underlying mechanism was determined via flow cytometric analysis, Western blot and rescue experiments. In addition, xenograft tumor model was constructed to verify the phenotypes upon CAPRIN1 silencing.Caprin-1 expression was significantly elevated in both ESCA tumor tissues and cell lines compared with that in normal adjacent tissues and fibroblasts. Increased CAPRIN1 mRNA expression was significantly associated with clinical prognosis and diagnostic accuracy. The GO enrichment and KEGG pathway analysis CAPRIN1 might be related to immune-related terms, protein binding processes, and metabolic pathways. A significant positive correlation was observed between high Caprin-1 protein levels and lymph node metastasis (P = 0.031), ki-67 (P = 0.023), and 18F- FDG PET/CT parameters (SUVmax (P = 0.002) and SUV mean (P = 0.005)) in 55 ESCA patients. At cut-off values of SUVmax 17.71 and SUVmean 10.14, 18F- FDG PET/CT imaging predicted Caprin-1 expression in ESCA samples with 70.8% sensitivity and 77.4% specificity. In vitro and in vivo assays showed that Caprin-1 knockdown affected ESCA tumor growth. Silencing Caprin-1 inhibited ESCA cell proliferation and glycolysis, and decreased the expression of methyltransferase-like 3 (METTL3) and Wilms' tumor 1-associating protein (WTAP). However, this effect could be partially reversed by the restoration of METTL3 and WTAP expression.Our data suggest that Caprin-1 could serve as a prognostic biomarker and has an oncogenic role in ESCA.© 2023. The Author(s).