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含71个三联基序的蛋白通过下调喉鳞状细胞癌中eIF5A2的表达来抑制肿瘤生长。

Tripartite Motif Containing 71 Suppresses Tumor Growth by Down-Regulating eIF5A2 Expression in Laryngeal Squamous Cell Carcinoma.

作者信息

Lou Dan, Wang Jianxing, Zhang Haizhong, Jia Qiaojing, Liu Lisha, Bian Yanrui, Di Yue, Shan Chunguang

机构信息

Department of Otolaryngology, the Second Hospital of Hebei Medical University, No. 215 Heping West Road, Shijiazhuang, 050000, Hebei, China.

Department of Otolaryngology, the First Hospital of Qinhuangdao, Qinhuangdao, 066000, Hebei, China.

出版信息

Appl Biochem Biotechnol. 2025 Mar;197(3):1504-1515. doi: 10.1007/s12010-024-05084-1. Epub 2024 Nov 23.

Abstract

The incidence of laryngeal squamous cell carcinoma (LSCC) has been rising recently. LSCC is one of the most prevalent malignant tumors of the head and neck. In this study, we aimed to investigate whether tripartite motif containing 71 (TRIM71) could serve as a molecular target for the treatment of LSCC. The mRNA and protein levels were examined by using real-time qPCR and Western blot, respectively. Cell proliferation was determined by cell-counting kit 8 assay. To further confirm the function of TRIM71 in LSCC, an in vivo cell line-derived xenograft study was conducted. The half-life of eukaryotic translation initiation factor 5A2 (eIF5A2) protein was measured by cycloheximide chase assay. Our results showed that TRIM71 was significantly downregulated in LSCC tumor tissues. TRIM71 overexpression significantly inhibited LSCC cell growth and suppressed tumor volume and weight in the xenograft models. The interaction between TRIM71 and eIF5A2 was verified by co-immunoprecipitation assay. Moreover, overexpression of TRIM71 in LSCC cells significantly inhibited the protein expression of eIF5A2 by down-regulating its stability, while it did not affect its mRNA level. In contrast, overexpression of eIF5A2 abolished the anti-tumor effects of TRIM71. In summary, TRIM71 may exert its anti-tumor effects through regulating eIF5A2, highlighting the potential of TRIM71 as an effective therapeutic target for the treatment of LSCC.

摘要

喉鳞状细胞癌(LSCC)的发病率近来一直在上升。LSCC是头颈部最常见的恶性肿瘤之一。在本研究中,我们旨在探究含三联基序蛋白71(TRIM71)是否可作为LSCC治疗的分子靶点。分别使用实时定量PCR和蛋白质免疫印迹法检测mRNA和蛋白质水平。通过细胞计数试剂盒8检测法测定细胞增殖。为进一步证实TRIM71在LSCC中的功能,进行了一项体内细胞系来源的异种移植研究。通过放线菌酮追踪试验测定真核翻译起始因子5A2(eIF5A2)蛋白的半衰期。我们的结果显示,TRIM71在LSCC肿瘤组织中显著下调。在异种移植模型中,TRIM71过表达显著抑制LSCC细胞生长,并抑制肿瘤体积和重量。通过免疫共沉淀试验验证了TRIM71与eIF5A2之间的相互作用。此外,LSCC细胞中TRIM71的过表达通过下调eIF5A2的稳定性显著抑制其蛋白表达,而不影响其mRNA水平。相反,eIF5A2的过表达消除了TRIM71的抗肿瘤作用。总之,TRIM71可能通过调节eIF5A2发挥其抗肿瘤作用,突出了TRIM71作为LSCC有效治疗靶点的潜力。

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