Department of Radiation Oncology, the First Affiliated Hospital of Bengbu Medical College, Zhihuai Road, Bengbu, 233000, Anhui, China.
Curr Protein Pept Sci. 2024;25(7):577-585. doi: 10.2174/0113892037287640240322084946.
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.
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.
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.
Our study underscores the multifaceted role of UBE2T in HNSC, illuminating its potential as a biomarker and therapeutic target.
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。
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。
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。
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。