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LncRNA-NEF 通过靶向 RUNX1 参与调控胃癌细胞增殖。

LncRNA‑NEF is involved the regulation of gastric carcinoma cell proliferation by targeting RUNX1.

机构信息

Department of General Surgery, Chengdu Fifth People's Hospital, Chengdu, Sichuan 611130, P.R. China.

Department of Dermatology, Chongqing First People's Hospital, Chongqing 400011, P.R. China.

出版信息

Mol Med Rep. 2019 Mar;19(3):2051-2056. doi: 10.3892/mmr.2019.9869. Epub 2019 Jan 16.

Abstract

Neighboring enhancer of FOXA2 (NEF) is a newly discovered long non‑coding RNA (lncRNA) that serves an oncogenic function in the metastasis of hepatocellular carcinoma, while its involvement in other types of cancer and in tumor cell proliferation remain unknown. In the present study, tumor tissues and adjacent healthy tissues were obtained from patients with gastric carcinoma, and blood was extracted from patients with gastric carcinoma and healthy controls. Expression of NEF in those tissues was detected using a reverse transcription‑quantitative polymerase chain reaction. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic value of serum lncRNA NEF for gastric carcinoma. All patients were followed‑up for 5 years following discharge, and survival curves were plotted to evaluate the diagnostic value of serum lncRNA‑NEF for gastric carcinoma. LncRNA‑NEF overexpression and small interfering RNA (siRNA) silencing cell lines were established and the effects on cell proliferation and runt‑related transcription factor 1 (Runx1) expression were detected using a Cell Counting Kit‑8 assay and western blot analysis, respectively. It was revealed that NEF was significantly downregulated in tumor tissues compared with in adjacent tissues. Levels of circulation NEF in serum were lower in patients with gastric carcinoma compared with in healthy controls, and were decreased with the increasing stages of primary tumor. Serum NEF is a sensitive diagnostic and prognostic marker for gastric carcinoma. NEF siRNA silencing promoted, and overexpression inhibited, gastric carcinoma proliferation. In addition, NEF overexpression promoted, and NEF siRNA silencing inhibited, Runx1 expression. Therefore, it was concluded that lncRNA NEF may participate in the regulation of cancer cell proliferation by regulating Runx1 expression.

摘要

邻近 FOXA2 增强子(NEF)是一种新发现的长链非编码 RNA(lncRNA),在肝细胞癌的转移中具有致癌功能,而其在其他类型癌症和肿瘤细胞增殖中的作用尚不清楚。在本研究中,从胃癌患者中获得肿瘤组织和相邻的健康组织,并从胃癌患者和健康对照者中提取血液。使用逆转录-定量聚合酶链反应检测这些组织中 NEF 的表达。通过绘制受试者工作特征曲线分析评估血清 lncRNA NEF 对胃癌的诊断价值。所有患者在出院后均进行了 5 年随访,并绘制生存曲线以评估血清 lncRNA-NEF 对胃癌的诊断价值。建立了 lncRNA-NEF 过表达和小干扰 RNA(siRNA)沉默细胞系,并使用细胞计数试剂盒-8 测定法和 Western blot 分析分别检测细胞增殖和 runt 相关转录因子 1(Runx1)表达的影响。结果表明,与相邻组织相比,肿瘤组织中 NEF 表达显著下调。与健康对照组相比,胃癌患者血清中循环 NEF 水平较低,且随着原发性肿瘤分期的增加而降低。血清 NEF 是胃癌的敏感诊断和预后标志物。NEF siRNA 沉默促进,而过表达抑制胃癌细胞增殖。此外,NEF 过表达促进,而 NEF siRNA 沉默抑制 Runx1 表达。因此,结论是 lncRNA NEF 可能通过调节 Runx1 表达参与调节癌细胞增殖。

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