Department of Hematology-Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, No.123, Dapi Rd., Niaosong Dist, Kaohsiung City, 833, Taiwan.
School of Medicine, Chung Shan Medical University, Taichung, 402, Taiwan.
BMC Cancer. 2021 Sep 1;21(1):979. doi: 10.1186/s12885-021-08726-3.
Ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX) has been identified as a histone 3 lysine 27 (H3K27) demethylase and acted as a tumor suppressor gene or oncogenic function. The current study was to explore the significance of UTX in oral tongue squamous cell carcinoma (OTSCC) patients who received surgical resection.
A total of 148 OTSCC patients who underwent surgical resection were identified, including 64 patients (43%) with overexpression of UTX and 84 patients (57%) harboring low expression of UTX. We also used two OTSCC cell lines, SAS and Cal 27, to determine the modulation of cancer. Chi-square test was used to investigate the difference of categorical variables between the groups; survival outcome was analyzed using the Kaplan-Meier method in univariate analysis, and a Cox regression model was performed for multivariate analyses.
Univariate and multivariate analyses showed overexpression of UTX were significantly related to worse disease-free survival (P = 0.028) and overall survival (P = 0.029). The two OTSCC cell lines were treated with GSK-J4, a potent inhibitor of UTX, and transwell migration and invasion assays showed an inhibitory effect with a dose-dependent manner. In addition, western blot analyses also revealed the inhibition of cell cycle and epithelial-mesenchymal transition.
Our study suggests that UTX plays an important role in the process of OTSCC and overexpression of UTX may predict poor prognosis in OTSCC patients who received surgical resection.
X 染色体上普遍转录的四肽重复序列(UTX)已被鉴定为组蛋白 3 赖氨酸 27(H3K27)去甲基酶,发挥抑癌基因或致癌作用。本研究旨在探讨接受手术切除的口腔舌鳞状细胞癌(OTSCC)患者中 UTX 的意义。
共鉴定了 148 例接受手术切除的 OTSCC 患者,包括 64 例(43%)UTX 过表达和 84 例(57%)UTX 低表达的患者。我们还使用了两种 OTSCC 细胞系 SAS 和 Cal 27,以确定癌症的调节。卡方检验用于组间分类变量差异的研究;单因素分析采用 Kaplan-Meier 法分析生存结果,多因素分析采用 Cox 回归模型。
单因素和多因素分析表明,UTX 过表达与无病生存率(P=0.028)和总生存率(P=0.029)显著相关。用 GSK-J4 处理两种 OTSCC 细胞系,一种有效的 UTX 抑制剂,transwell 迁移和侵袭实验显示出剂量依赖性的抑制作用。此外,Western blot 分析还揭示了细胞周期和上皮间质转化的抑制作用。
我们的研究表明,UTX 在 OTSCC 过程中发挥重要作用,UTX 过表达可能预示着接受手术切除的 OTSCC 患者预后不良。