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泛素连接酶 E2 T 的敲低通过抑制 NF-Κb 信号通路和诱导铁死亡来阻止头颈部鳞状细胞癌的进展。

Knockdown of Ubiquitin-Conjugating Enzyme E2 T Abolishes the Progression of Head and Neck Squamous Cell Carcinoma by Inhibiting NF-Κb Signaling and inducing Ferroptosis.

机构信息

Department of Radiation Oncology, the First Affiliated Hospital of Bengbu Medical College, Zhihuai Road, Bengbu, 233000, Anhui, China.

出版信息

Curr Protein Pept Sci. 2024;25(7):577-585. doi: 10.2174/0113892037287640240322084946.

DOI:10.2174/0113892037287640240322084946
PMID:38584528
Abstract

BACKGROUND

Ubiquitin-conjugating enzyme 2T (UBE2T) has been reported to be associated with uncontrolled cell growth and tumorigenesis in multiple cancer types. However, the understanding of its regulatory role in the carcinogenesis of Head And Neck Squamous Cell Carcinoma (HNSC) is limited.

METHODS

UBE2T expression in HNSC patient samples and the correlation between its expression and patients' survival rates were evaluated using The Cancer Genome Atlas (TCGA) database. Cell survival and proliferation were investigated in UM-SCC1 and UM-SCC15 cells infected with control and shUBE2T lentivirus. The xenograft mouse model was established using UM-SCC15 cells to examine HNSC tumorigenesis with or without UBE2T. Western blot, qRT-PCR, and ferroptosis assays were carried out to disclose the interaction between UBE2T and NF-κB signaling and ferroptosis.

RESULTS

The increased expression of UBE2T was noted in tumor tissues of patients with HNSC, correlating with a significantly reduced overall survival time in this patient cohort. Knockdown of UBE2T inhibited HNSC tumorigenesis and tumor growth. Mechanistically, inhibition of UBE2T suppressed NF-κB signaling and induced ferroptosis in HNSC.

CONCLUSION

Our study underscores the multifaceted role of UBE2T in HNSC, illuminating its potential as a biomarker and therapeutic target.

摘要

背景

泛素连接酶 2T(UBE2T)已被报道与多种癌症类型中的失控细胞生长和肿瘤发生有关。然而,其在头颈部鳞状细胞癌(HNSC)发生中的调控作用的理解是有限的。

方法

使用癌症基因组图谱(TCGA)数据库评估 UBE2T 在 HNSC 患者样本中的表达及其与患者生存率之间的相关性。通过感染对照和 shUBE2T 慢病毒的 UM-SCC1 和 UM-SCC15 细胞来研究细胞存活和增殖。使用 UM-SCC15 细胞建立异种移植小鼠模型,以检查有无 UBE2T 时 HNSC 的肿瘤发生。进行 Western blot、qRT-PCR 和铁死亡测定,以揭示 UBE2T 与 NF-κB 信号和铁死亡之间的相互作用。

结果

在 HNSC 患者的肿瘤组织中观察到 UBE2T 的表达增加,与该患者队列的总生存时间显著降低相关。UBE2T 的敲低抑制了 HNSC 的肿瘤发生和肿瘤生长。机制上,UBE2T 的抑制抑制了 NF-κB 信号并诱导了 HNSC 中的铁死亡。

结论

我们的研究强调了 UBE2T 在 HNSC 中的多方面作用,阐明了其作为生物标志物和治疗靶标的潜力。

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Epidemiology, Risk Factors, and Prevention of Head and Neck Squamous Cell Carcinoma.头颈部鳞状细胞癌的流行病学、危险因素和预防。
Med Sci (Basel). 2023 Jun 13;11(2):42. doi: 10.3390/medsci11020042.
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Identification of SLC2A3 as a prognostic indicator correlated with the NF-κB/EMT axis and immune response in head and neck squamous cell carcinoma.鉴定 SLC2A3 作为一个与 NF-κB/EMT 轴和头颈部鳞状细胞癌免疫反应相关的预后指标。
Channels (Austin). 2023 Dec;17(1):2208928. doi: 10.1080/19336950.2023.2208928.
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Pan-cancer analysis of UBE2T with a focus on prognostic and immunological roles in lung adenocarcinoma.
UBE2T 通过泛素化 PBX1 和 PBX1/RORA 调控促进 I 期肺腺癌进展。
BMC Cancer. 2024 Sep 18;24(1):1158. doi: 10.1186/s12885-024-12887-2.
泛癌症分析 UBE2T,重点是肺腺癌中的预后和免疫作用。
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Immunotherapy in head and neck squamous cell carcinoma: An updated review.头颈部鳞状细胞癌的免疫治疗:最新综述
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Prognostic Value of UBE2T and Its Correlation with Immune Infiltrates in Lung Adenocarcinoma.UBE2T在肺腺癌中的预后价值及其与免疫浸润的相关性
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UBE2T/STAT3 Signaling Promotes the Proliferation and Tumorigenesis in Retinoblastoma.UBE2T/STAT3 信号促进视网膜母细胞瘤的增殖和肿瘤发生。
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ANLN and UBE2T are prognostic biomarkers associated with immune regulation in breast cancer: a bioinformatics analysis.ANLN和UBE2T是与乳腺癌免疫调节相关的预后生物标志物:一项生物信息学分析。
Cancer Cell Int. 2022 May 16;22(1):193. doi: 10.1186/s12935-022-02611-0.
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Review: NF-kB activation in canine cancer.综述:犬科癌症中的 NF-κB 激活。
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Expression and prognostic analysis of BGN in head and neck squamous cell carcinoma.BGN 在头颈部鳞状细胞癌中的表达及预后分析。
Gene. 2022 Jun 15;827:146461. doi: 10.1016/j.gene.2022.146461. Epub 2022 Mar 28.
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