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TRAIP通过与DDX39A相互作用,经上皮-间质转化和Wnt/β-连环蛋白信号通路促进舌鳞状细胞癌进展。

TRAIP enhances progression of tongue squamous cell carcinoma through EMT and Wnt/β-catenin signaling by interacting with DDX39A.

作者信息

Liu Litong, Wang Ping, Guo Cheng, Song Li, Chen Lifang, Qi Hongbing, Zheng Yangyang, Xing Xiaoming, Wang Chengqin

机构信息

Department of Pathology, School of Basic Medicine, Qingdao University, Ningxia Road No. 308, Qingdao, Shandong, 266071, China.

Department of Pathology, Linyi People's Hospital, Linyi, 276000, Shandong, China.

出版信息

BMC Cancer. 2024 Dec 2;24(1):1481. doi: 10.1186/s12885-024-13130-8.

Abstract

BACKGROUND

Tongue squamous cell carcinoma (TSCC) is one of the most common malignant tumors with high mortality and poor prognosis. Its incidence rate is increasing gradually. Tumor necrosis factor receptor-associated factor interacting protein (TRAIP), as a factor related to several tumors, reveals that its gene expression is different between normal tissue and primary tumor of head and neck squamous cell carcinoma using bioinformatics analysis.

METHOD

In our study, TCGA database, immunohistochemistry, proliferation assay, colony formation, wound healing assay, Transwell, cell cycle analysis and tumor xenografts model were used to determine the expression and functions of TRAIP in TSCC.

RESULT

We found that TRAIP may promote the proliferation, migration and invasion of TSCC. Furthermore, the results of bioinformatics analysis, mass spectrometry and co-immunoprecipitation suggested that DDX39A may be a TRAIP interacting protein. DDX39A has been proven to be an oncogene in several tumors, which may have an important effect on cell proliferation and metastasis in multiple tumors. In addition, the high expression of DDX39A implies the poor prognosis of patients. Our study demonstrated that TRAIP probably interact with DDX39A to regulate cell progression through epithelial-mesenchymal transition and Wnt/β-catenin pathway. In addition, we show that the necessary domain of DDX39A for the interaction between DDX39A and TRAIP region.

CONCLUSION

These results indicate that TRAIP is important in occurrence and development of TSCC and is expected to become the new promising therapeutic target.

摘要

背景

舌鳞状细胞癌(TSCC)是最常见的恶性肿瘤之一,死亡率高且预后差。其发病率正在逐渐上升。肿瘤坏死因子受体相关因子相互作用蛋白(TRAIP)作为一种与多种肿瘤相关的因子,通过生物信息学分析显示其在正常组织与头颈部鳞状细胞癌原发肿瘤之间的基因表达存在差异。

方法

在我们的研究中,使用TCGA数据库、免疫组织化学、增殖试验、集落形成、伤口愈合试验、Transwell试验、细胞周期分析和肿瘤异种移植模型来确定TRAIP在TSCC中的表达及功能。

结果

我们发现TRAIP可能促进TSCC的增殖、迁移和侵袭。此外,生物信息学分析、质谱分析和免疫共沉淀的结果表明DDX39A可能是TRAIP的相互作用蛋白。DDX39A已被证实在多种肿瘤中是一种癌基因,可能对多种肿瘤的细胞增殖和转移具有重要影响。此外,DDX39A的高表达意味着患者预后不良。我们的研究表明,TRAIP可能与DDX39A相互作用,通过上皮-间质转化和Wnt/β-连环蛋白途径调节细胞进程。此外,我们展示了DDX39A与TRAIP区域相互作用所需的结构域。

结论

这些结果表明TRAIP在TSCC的发生和发展中起重要作用,有望成为新的有前景的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/108b/11610093/28ea5c942d69/12885_2024_13130_Fig1_HTML.jpg

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