Department of Pathology, Beijing Key Laboratory of Head and Neck Molecular Diagnostic Pathology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, P.R. China.
Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, P.R. China.
Oncol Rep. 2017 Nov;38(5):3019-3029. doi: 10.3892/or.2017.5976. Epub 2017 Sep 20.
Solute carrier family 7, membrane 11 (SLC7A11) or (xCT) is a component of the cysteine-glutamate transporter, which plays a critical role in glutathione homeostasis which is important to protect cells from oxidative stress. SLC7A11 is distributed in various tissues and participates in the occurrence of a number of diseases, particularly in the pathogenesis of malignant tumors, but its role in laryngeal cancer development has not yet been clearly defined. The objective of the present study was to investigate the role of SLC7A11 in laryngeal squamous cell carcinoma (LSCC). We conducted immunohistochemistry and RT-PCR to evaluate the protein and mRNA levels of SLC7A11 in LSCC and in control tissues, respectively. The knockdown experiments were conducted with SLC7A11 short hairpin RNA (shRNA) lentivirus, and the protein and mRNA levels of SLC7A11 were assessed by RT-PCR and western blotting. The functional study of SLC7A11 in vitro was conducted by MTT assay, and the effects on the cell cycle were detected using flow cytometry. Immunohistochemical results revealed that the expression levels of SLC7A11, Ki-67 and p53 in LSCC tissues were higher than those in laryngeal dysplasia tissues. The Spearman rank correlation analysis revealed that the expression of SLC7A11 was positively correlated with the expression of p53 and Ki-67. Cox regression analysis and Kaplan-Meier plots confirmed that the expression levels of SLC7A11 were a prognostic factor for overall survival (OS) rates and postoperative recurrence of LSCC. Moreover, the functional study of SLC7A11 in vitro revealed that knockdown of SLC7A11 using shRNA inhibited cell proliferation by inducing cell cycle arrest at the G1 phase. Immunohistochemical and RT-PCR results and knockdown experiments of SLC7A11 revealed that SLC7A11 was involved in the progression of LSCC, and may provide clinical information for the evaluation of OS rates and postoperative recurrence of LSCC. Collectively, these observations suggest that SLC7A11 may be a vital biomarker for the diagnosis and prognosis in human LSCC, and targeting SLC7A11 appears to be a potentially significant method for LSCC treatment.
溶质载体家族 7，膜 11（SLC7A11）或（xCT）是胱氨酸-谷氨酸转运体的组成部分，在谷胱甘肽稳态中发挥关键作用，这对于保护细胞免受氧化应激至关重要。SLC7A11 分布于各种组织中，并参与多种疾病的发生，特别是恶性肿瘤的发病机制，但它在喉癌发展中的作用尚未明确。本研究旨在探讨 SLC7A11 在喉鳞状细胞癌（LSCC）中的作用。我们分别通过免疫组织化学和 RT-PCR 评估了 LSCC 及对照组织中 SLC7A11 的蛋白和 mRNA 水平。利用 SLC7A11 短发夹 RNA（shRNA）慢病毒进行敲低实验，并通过 RT-PCR 和 Western blot 评估 SLC7A11 的蛋白和 mRNA 水平。通过 MTT 测定法进行 SLC7A11 的体外功能研究，并通过流式细胞术检测对细胞周期的影响。免疫组织化学结果显示，LSCC 组织中 SLC7A11、Ki-67 和 p53 的表达水平高于喉发育不良组织。Spearman 等级相关分析显示 SLC7A11 的表达与 p53 和 Ki-67 的表达呈正相关。Cox 回归分析和 Kaplan-Meier 图证实 SLC7A11 的表达水平是 LSCC 总生存率（OS）和术后复发的预后因素。此外，SLC7A11 的体外功能研究显示，使用 shRNA 敲低 SLC7A11 通过诱导 G1 期细胞周期停滞抑制细胞增殖。SLC7A11 的免疫组织化学和 RT-PCR 结果以及敲低实验表明 SLC7A11 参与 LSCC 的进展，并且可能为 LSCC 的 OS 率和术后复发的评估提供临床信息。综上所述，这些观察结果表明 SLC7A11 可能是人类 LSCC 诊断和预后的重要生物标志物，靶向 SLC7A11 似乎是 LSCC 治疗的一种有潜力的方法。
