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TRIM24 过表达促进头颈部鳞状细胞癌的增殖和葡萄糖代谢。

Overexpression of TRIM24 Stimulates Proliferation and Glucose Metabolism of Head and Neck Squamous Cell Carcinoma.

机构信息

Department of Otolaryngology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.

Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.

出版信息

Biomed Res Int. 2018 May 10;2018:6142843. doi: 10.1155/2018/6142843. eCollection 2018.

Abstract

TRIM24 (Tripartite Motif Containing 24) is a recently identified oncogene overexpressed in various cancers. However, the molecular mechanism of TRIM24 in the progression of head and neck squamous cell carcinoma (HNSCC) remains ambiguous. In the present study, we analyzed the expression pattern of TRIM24 in 100 HNSCC tissues and found that TRIM24 was overexpressed in 43/100 HNSCC cases. Significant association was found between TRIM24 overexpression and tumor-node-metastasis (TNM) stage ( = 0.0034) and T stage ( = 0.0048). Furthermore, we overexpressed and knocked down TRIM24 in Detroit 562 and FaDu cell lines, respectively. TRIM24 overexpression promoted proliferation, colony formation, and invasion, while TRIM24 depletion inhibited proliferation, colony formation, and invasion. Further studies showed that TRIM24 facilitated cell cycle transition and upregulated cyclin D1 and p-Rb. In addition, we found that GLUT3, a key protein involved in regulating glucose metabolism, was altered in HNSCC cells overexpressing TRIM24. We demonstrated that TRIM24 overexpression increased glucose uptake ATP production. Overexpression of TRIM24 increases cell sensitivity to glucose deprivation in Detroit cells. Depleting TRIM24 in FaDu cells demonstrated the opposite results. We also showed that TRIM24 could bind to the promoter region of cyclin D1. In conclusion, TRIM24 is upregulated in HNSCC and promotes HNSCC cell growth and invasion through modulation of cell cycle, glucose metabolism, and GLUT3, making TRIM24 a potential oncoprotein in HNSCC.

摘要

TRIM24(三部分基序包含 24 个)是一种最近在多种癌症中发现的过表达癌基因。然而,TRIM24 在头颈部鳞状细胞癌(HNSCC)进展中的分子机制尚不清楚。在本研究中,我们分析了 100 例 HNSCC 组织中 TRIM24 的表达模式,发现 43/100 例 HNSCC 中 TRIM24 过表达。TRIM24 过表达与肿瘤-淋巴结-转移(TNM)分期(=0.0034)和 T 分期(=0.0048)显著相关。此外,我们分别在 Detroit 562 和 FaDu 细胞系中转染了 TRIM24。TRIM24 过表达促进了增殖、集落形成和侵袭,而 TRIM24 敲低则抑制了增殖、集落形成和侵袭。进一步的研究表明,TRIM24 促进了细胞周期的转变,并上调了 cyclin D1 和 p-Rb。此外,我们发现 GLUT3,一种参与调节葡萄糖代谢的关键蛋白,在过表达 TRIM24 的 HNSCC 细胞中发生了改变。我们证明,TRIM24 过表达增加了葡萄糖摄取和 ATP 产生。TRIM24 在 Detroit 细胞中的过表达增加了细胞对葡萄糖剥夺的敏感性。在 FaDu 细胞中敲低 TRIM24 则得到了相反的结果。我们还表明,TRIM24 可以与 cyclin D1 的启动子区域结合。总之,TRIM24 在 HNSCC 中上调,并通过调节细胞周期、葡萄糖代谢和 GLUT3 促进 HNSCC 细胞的生长和侵袭,使 TRIM24 成为 HNSCC 中的一种潜在癌蛋白。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c51/5971268/3959d114355f/BMRI2018-6142843.001.jpg

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