Department of Gastroenterology, 38044The Affiliated Jiangyin Hospital of Xuzhou Medical University, Jiangyin, People's Republic of China.
School of Radiation Medicine and Protection and State Key Laboratory of Radiation Medicine and Protection, 74565Medical College of Soochow University, Suzhou, People's Republic of China.
Technol Cancer Res Treat. 2020 Jan-Dec;19:1533033820973282. doi: 10.1177/1533033820973282.
Esophageal cancer is one of the most common malignancies worldwide. Ubiquitin-dependent degradation of regulatory proteins reportedly plays a central role in diverse cellular processes. This study investigated the expression levels of ubiquitin in esophageal squamous cell carcinoma tissues and the functions of ubiquitin in the context of esophageal squamous cell carcinoma progression.
The expression of ubiquitin in esophageal squamous cell carcinoma and normal esophageal samples was determined via immunohistochemistry. Serum ubiquitin levels were determined by enzyme-linked immunosorbent assay. The association between serum ubiquitin level and clinicopathological factors was analyzed. Real-time PCR analysis was employed to measure the mRNA levels of the ubiquitin coding genes and . Proliferation assays, colony formation assays, and Transwell-based assays were used to determine the influence of ubiquitin on cell growth and cell invasion. Proteomic analysis was performed to identify the proteins associated with ubiquitin.
Ubiquitin expression in esophageal squamous cell carcinoma tissues was markedly higher than that in normal and tumor adjacent tissues. The levels of ubiquitin in esophageal squamous cell carcinoma serum samples were significantly higher than those in healthy controls. Serum ubiquitin levels were correlated with tumor stage and lymph node metastasis. To silence the expression of ubiquitin, we knocked down the ubiquitin coding genes and in TE-1 and Eca-109 cells. Silencing ubiquitin resulted in the suppression of cell growth, chemoresistance, colony formation and cell migration in esophageal squamous cell carcinoma cells. Proteomic analysis in esophageal squamous cell carcinoma cells showed that knockdown of ubiquitin coding genes deregulated the expression of 159 proteins (92 were upregulated and 67 were downregulated) involved in multiple pathways. These proteins included ferritin light chain, ferritin heavy chain, cellular retinoic acid-binding protein 2, and DNA replication factor 1.
Ubiquitin expression is upregulated in esophageal squamous cell carcinoma tissues and serum samples. Serum ubiquitin levels were correlated with tumor stage and lymph node metastasis. Downregulation of ubiquitin suppresses the aggressive phenotypes of esophageal squamous cell carcinoma cells by complex mechanisms; ubiquitin may represent a novel target for the treatment of esophageal squamous cell carcinoma.
食管癌是全球最常见的恶性肿瘤之一。据报道，调节蛋白的泛素依赖性降解在多种细胞过程中起着核心作用。本研究旨在探讨泛素在食管鳞状细胞癌组织中的表达水平，以及泛素在食管鳞状细胞癌进展过程中的功能。
通过免疫组织化学法检测食管鳞状细胞癌和正常食管组织中泛素的表达。采用酶联免疫吸附试验检测血清泛素水平。分析血清泛素水平与临床病理因素的关系。采用实时 PCR 分析测定泛素编码基因 和 的 mRNA 水平。增殖试验、集落形成试验和 Transwell 侵袭试验用于测定泛素对细胞生长和细胞侵袭的影响。进行蛋白质组学分析以鉴定与泛素相关的蛋白质。
食管鳞状细胞癌组织中泛素的表达明显高于正常和肿瘤旁组织。食管鳞状细胞癌血清样本中的泛素水平明显高于健康对照组。血清泛素水平与肿瘤分期和淋巴结转移相关。为了沉默泛素的表达，我们敲低了 TE-1 和 Eca-109 细胞中的泛素编码基因 和 。沉默泛素导致食管鳞状细胞癌细胞生长、化疗耐药、集落形成和细胞迁移受到抑制。食管鳞状细胞癌细胞中的蛋白质组学分析显示，敲低泛素编码基因使 159 种蛋白质（92 种上调，67 种下调）的表达失调，这些蛋白质涉及多个途径，包括铁蛋白轻链、铁蛋白重链、细胞视黄醇结合蛋白 2 和 DNA 复制因子 1。
泛素在食管鳞状细胞癌组织和血清样本中表达上调。血清泛素水平与肿瘤分期和淋巴结转移相关。下调泛素通过复杂机制抑制食管鳞状细胞癌细胞的侵袭表型；泛素可能成为治疗食管鳞状细胞癌的新靶点。
