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中国癌症防治杂志 ›› 2025, Vol. 17 ›› Issue (3): 383-390.doi: 10.3969/j.issn.1674-5671.2025.03.17

• 头颈部肿瘤专栏 • 上一篇    下一篇

USP41通过去泛素化STAT1调控头颈部鳞状细胞癌恶性生物学行为

  

  1. 内蒙古医科大学附属医院耳鼻咽喉科;国药北方医院耳鼻咽喉科
  • 出版日期:2025-06-25 发布日期:2025-07-10
  • 通讯作者: 白云飞 E-mail:baiyunfei007@sina.com
  • 基金资助:
    内蒙古自治区自然科学基金项目(2023LHMS08021)

USP41 modulates the malignant biological behaviors of head and neck squamous cell carcinoma through the deubiquitination of STAT1#br#

  • Online:2025-06-25 Published:2025-07-10

摘要: 目的 探讨泛素特异性肽酶41(ubiquitin specific peptidase 41,USP41)调控头颈部鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)恶性生物学行为的分子机制。方法 利用基因表达谱交互分析(gene expression profiling interactive analysis,GEPIA)数据库分析USP41在HNSCC等肿瘤中的表达谱。体外培养HNSCC细胞系(UM2、UM1和HN31)及正常口腔角质细胞HOK,通过质粒转染技术,采用shRNA敲低USP41(shRNA #1/#2)或过表达信号转导子和转录激活子1(signal transducer and activator of transcription 1,STAT1)/USP41,同时设置相应空载体对照。采用RT⁃qPCR检测USP41、上皮⁃间质转化(epithelial⁃mesenchymal transition,EMT)标志物(E⁃cadherin、Vimentin和N⁃cadherin)和STAT1的mRNA表达;Western blot检测USP41、STAT1蛋白表达及泛素化水平;CCK⁃8、克隆形成和Transwell实验检测细胞增殖、迁移和侵袭能力;利用免疫共沉淀和Western blot验证UM1细胞中USP41与STAT1的相互作用。结果 USP41在HNSCC等多种肿瘤中表达上调(均P<0.05)。在UM1和HN31细胞中USP41 mRNA和蛋白表达上调(均P<0.05);敲低USP41可抑制细胞增殖、迁移和侵袭,并使E⁃cadherin表达上调,而Vimentin、N⁃cadherin表达降低(均P<0.01),过表达STAT1则可逆转该结果。过表达USP41可降低UM1细胞泛素化蛋白水平,并上调STAT1和USP41蛋白表达水平。免疫共沉淀和Western blot实验证实USP41和STAT1在UM1细胞中存在相互作用。结论 USP41在HNSCC细胞中呈高表达,并通过STAT1的去泛素化促进HNSCC细胞增殖、迁移、侵袭及EMT进程,有望成为HNSCC治疗的潜在靶点。

关键词: 头颈部鳞状细胞癌, 去泛素化, 泛素特异性肽酶41, 信号转导子和转录激活子1, 细胞增殖, 上皮?间质转化

Abstract: Objective To elucidate the molecular mechanisms through which ubiquitin⁃specific peptidase 41 (USP41) modulates the malignant biological behavior of head and neck squamous cell carcinoma (HNSCC). Methods The Gene Expression Profiling Interactive Analysis (GEPIA) database was used to examine expression profiling of USP41 across various tumors, including HNSCC. HNSCC cells lines (UM2, UM1, and HN31), along with normal oral keratinocyte (HOK) cells were cultured in vitro. Plasmid transfections were conducted to achieve knockdown of USP41 utilizing shRNA constructs (shRNA#1 and shRNA#2) and to facilitate the overexpression of signal transducer and activator of transcription 1 (STAT1). and USP41. Corresponding empty vector controls were included concurrently. Reverse transcription quantitative polymerase chain reaction (RT⁃qPCR) was used to quantify the mRNA expression levels of USP41, epithelial⁃mesenchymal transition (EMT) markers (E⁃cadherin, vimentin, and N⁃cadherin), and STAT1. Western blot analysis was used to determine the protein expression and ubiquitination levels of USP41and STAT1. Cell Counting Kit⁃8 (CCK⁃8), colony formation, and Transwell assays were conducted to assess the cells proliferation, migration, and invasion capabilities. Co⁃immunoprecipitation combined with Western blot analysis was used to validate the interaction between USP41 and STAT1 in UM1 cells. Results USP41 expression was upregulated in various tumor types, including HNSCC (P<0.05). Both mRNA and protein levels of USP41 were elevated in UM1 and HN31 cell lines (all P<0.05). Knockdown of USP41 resulted in the inhibition of cell proliferation, migration and invasion, accompanied by an increase in E⁃cadherin expression and a decrease Vimentin and N⁃cadherin expression (all P<0.01). These effects were reversed upon overexpression of STAT1. USP41 overexpression led to a reduction in  ubiquitinated protein levels while enhancing the expression of STAT1 and USP41 protein in UM1 cell lines. Co⁃immunoprecipitation and Western blot confirmed the interaction between USP41 and STAT1 in UM1 cell lines. Conclusions USP41 is markedly overexpressed in HNSCC cell lines and facilitates cell proliferation, migration, invasion, and EMT progression through STAT1 deubiquitination, suggesting its potential as a therapeutic target for HNSCC.

Key words:  Head and neck squamous cell carcinoma, Deubiquitination, Ubiquitin?specific peptidase 41, Sigal transducer and activtor of transcription, Cell proliferation, Epithelial?mesenchymal transition

中图分类号: 

  • R739.91