长链非编码 RNA-NEF 通过抑制 wnt/β-连环蛋白通路抑制食管鳞状细胞癌细胞的增殖、迁移和侵袭。
LncRNA-NEF inhibits proliferation, migration and invasion of esophageal squamous-cell carcinoma cells by inactivating wnt/β-catenin pathway.
机构信息
Department of Gastroenterology, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang City, Hubei Province, PR. China.
出版信息
Eur Rev Med Pharmacol Sci. 2018 Oct;22(20):6824-6831. doi: 10.26355/eurrev_201810_16150.
OBJECTIVE
Our study aimed to investigate the role of lncRNA-Neighboring Enhancer of FOXA2 (NEF) in esophageal squamous-cell carcinoma.
PATIENTS AND METHODS
Tumor tissues and adjacent tissues were obtained from esophageal squamous-cell carcinoma patients, and blood samples were extracted from both patients with esophageal squamous-cell carcinoma and healthy volunteers. The expression of NEF was detected by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). All patients were followed-up for 5 years and ROC curve analysis and survival analysis were performed to evaluate the diagnostic and prognostic values of serum NEF for esophageal squamous-cell carcinoma. NEF expression vector was transfected into cells of esophageal squamous-cell carcinoma cell lines. Cell proliferation, migration and invasion were detected by CCK-8 assay, transwell migration assay, and transwell invasion assay, respectively. The interaction between NEF and wnt/β-catenin pathway were explored by Western blot and qRT-PCR.
RESULTS
Expression of NEF was significantly downregulated in tumor tissues than in adjacent tissues in most patients. Serum level of NEF was higher in esophageal squamous-cell carcinoma patients than in healthy controls, and was significantly correlated with tumor size and tumor distant tumor metastasis. Serum NEF is a promising diagnostic and prognostic marker for esophageal squamous-cell carcinoma. NEF overexpression inhibited cancer cell proliferation, migration and invasion. NEF overexpression decreased the expression levels of wnt/β-catenin pathway-related proteins, while Wnt activator showed no significant effects on NEF. However, Wnt inhibitor reduced the effects of NEF overexpression on cell proliferation, migration and invasion.
CONCLUSIONS
LncRNA NEF may inhibit the proliferation, migration and invasion of esophageal squamous-cell carcinoma cells by inactivating with wnt/β-catenin pathway.
目的
本研究旨在探讨长链非编码 RNA-邻近 FOXA2 增强子（NEF）在食管鳞状细胞癌中的作用。
患者和方法
从食管鳞状细胞癌患者中获取肿瘤组织和相邻组织，并从食管鳞状细胞癌患者和健康志愿者中提取血液样本。通过实时定量聚合酶链反应（qRT-PCR）检测 NEF 的表达。对所有患者进行 5 年随访，通过 ROC 曲线分析和生存分析评估血清 NEF 对食管鳞状细胞癌的诊断和预后价值。将 NEF 表达载体转染到食管鳞状细胞癌细胞系的细胞中。通过 CCK-8 测定、Transwell 迁移测定和 Transwell 侵袭测定分别检测细胞增殖、迁移和侵袭。通过 Western blot 和 qRT-PCR 探讨 NEF 与 wnt/β-catenin 通路的相互作用。
结果
在大多数患者中，肿瘤组织中 NEF 的表达明显低于相邻组织。食管鳞状细胞癌患者血清 NEF 水平高于健康对照组，且与肿瘤大小和远处转移明显相关。血清 NEF 是一种有前途的诊断和预后标志物，可用于食管鳞状细胞癌。NEF 过表达抑制癌细胞增殖、迁移和侵袭。NEF 过表达降低了 wnt/β-catenin 通路相关蛋白的表达水平，而 Wnt 激活剂对 NEF 没有明显影响。然而，Wnt 抑制剂降低了 NEF 过表达对细胞增殖、迁移和侵袭的影响。
结论
LncRNA NEF 可能通过抑制 wnt/β-catenin 通路来抑制食管鳞状细胞癌细胞的增殖、迁移和侵袭。
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