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

Zhichao Hou,Madiniyat Niyaz,Lei Wang,Idiris Awut,Abulajiang Abuduerheman,Halmurat Upur,Ilyar Sheyhidin,Ayshamgul Hasim,Haiping Zhang

doi:10.3892/ijo.2018.4253

Abstract

Ring finger protein113A (RNF113A) possesses a C3HC4 zinc finger domain and this domain is found in E3ubiquitin 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 117patients with ESCC were selected, as well as 41pairs 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 Tclassification (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 (Nclassification). 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 invitro, and RNF113A silencing reversed these malignant behaviors. RNF113A knockdown inhibited tumor growth invivo. 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.

Highlights

Ring finger protein 113A (RNF113A) expression was positive in 64.1% (75/117) of the esophageal squamous cell carcinoma (ESCC) samples
enzyme 3 (E3) ligases are involved in Snail and Twist ubiquitination, which play important roles in epithelial-mesenchymal transition (EMT) [10,11]
RNF113A has a RING domain [14], which is frequently found in E3 ubiquitin ligases

Summary

Introduction

Esophageal cancer (EC) is the sixth leading cause of cancer‐related mortality worldwide [1]. In China, EC is ranked as the fourth leading cause of cancer-related mortality, and an estimated 218,957 individuals succumbed to the disease in China in 2011 [2]. In China, the majority of EC cases are esophageal squamous cell carcinoma (ESCC) [3]. 80% of ESCC cases occur in the Central and South-East Asian region. China alone contributes to more than half of the global cases (53%, 210,000 cases) [5]. A distinctive characteristic of EC in China is its uneven burden between rural and urban areas. The rates of EC are 2- to 10-fold higher in rural areas compared with urban areas [2]

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