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RNF113A 促进食管鳞癌细胞的增殖、迁移和侵袭,并与不良预后相关。

RNF113A promotes the proliferation, migration and invasion, and is associated with a poor prognosis of esophageal squamous cell carcinoma.

机构信息

Department of Thoracic Surgery, Τhe First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region 830054, P.R. China.

Department of Pathology, Medical University of Xinjiang, Urumqi, Xinjiang Uygur Autonomous Region 830054, P.R. China.

出版信息

Int J Oncol. 2018 Mar;52(3):861-871. doi: 10.3892/ijo.2018.4253. Epub 2018 Jan 24.

DOI:10.3892/ijo.2018.4253
PMID:29393393
Abstract

Ring finger protein 113A (RNF113A) possesses a C3HC4 zinc finger domain and this domain is found in E3 ubiquitin ligase and is involved in tumorigenesis. To date, and at least to the best of our knowledge, there are no studies available which have investigated RNF113A in cancer. Thus, this study aimed to explore the role of RNF113A in the development of esophageal squamous cell carcinoma (ESCC). For this purpose, paraffin-embedded samples from 117 patients with ESCC were selected, as well as 41 pairs of fresh-frozen ESCC and adjacent normal tissue samples. RNF113A expression was examined by immunohistochemistry and reverse transcription-quantitative PCR (RT-qPCR). RNF113A was overexpressed or silenced in the EC9706 and Eca109 cells. The cells were examined for cell cycle progression, apoptosis, invasiveness and migration. Xenograft tumors were also created in mice using the Eca109 cells. Tumor differentiation (P=0.008) and T classification (P<0.001) were found to be significantly associated with RNF113A expression. No statistically significant association was observed between RNF113A expression and sex, age, histological type, tumor location and lymph node metastasis (N classification). Kaplan-Meier analysis revealed that the patients with ESCC with ahigh expression of RNF113A had a lower survival rate than those with a low expression (P=0.002). Multivariate analysis revealed that RNF113A expression (HR=2.406; 95% CI, 1.301-4.449, P=0.005) was independently associated with overall survival in patients with ESCC. The overexpression of RNF113A promoted proliferation, migration, and invasiveness of ESCC cell lines in vitro, and RNF113A silencing reversed these malignant behaviors. RNF113A knockdown inhibited tumor growth in vivo. Thus, these results indicate that RNF113A promotes the proliferation, migration and invasiveness of ESCC cell lines. RNF113A expression in ESCC is this associated with a poor prognosis of affected patients.

摘要

环指蛋白 113A(RNF113A)具有 C3HC4 锌指结构域,该结构域存在于 E3 泛素连接酶中,并参与肿瘤发生。迄今为止,至少据我们所知,尚无研究探讨 RNF113A 在癌症中的作用。因此,本研究旨在探讨 RNF113A 在食管鳞状细胞癌(ESCC)发展中的作用。为此,选择了 117 例 ESCC 患者的石蜡包埋样本,以及 41 对新鲜冷冻的 ESCC 及相邻正常组织样本。采用免疫组织化学和逆转录定量 PCR(RT-qPCR)检测 RNF113A 的表达。在 EC9706 和 Eca109 细胞中过表达或沉默 RNF113A。检测细胞周期进展、凋亡、侵袭和迁移。还使用 Eca109 细胞在小鼠中创建了异种移植肿瘤。肿瘤分化(P=0.008)和 T 分类(P<0.001)与 RNF113A 表达显著相关。RNF113A 表达与性别、年龄、组织学类型、肿瘤位置和淋巴结转移(N 分类)之间无统计学关联。Kaplan-Meier 分析显示,RNF113A 高表达的 ESCC 患者的生存率低于低表达患者(P=0.002)。多变量分析显示,RNF113A 表达(HR=2.406;95%CI,1.301-4.449,P=0.005)与 ESCC 患者的总生存独立相关。RNF113A 的过表达促进了 ESCC 细胞系在体外的增殖、迁移和侵袭,而 RNF113A 的沉默逆转了这些恶性行为。RNF113A 敲低抑制了体内肿瘤的生长。因此,这些结果表明 RNF113A 促进 ESCC 细胞系的增殖、迁移和侵袭。RNF113A 在 ESCC 中的表达与患者的不良预后相关。

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