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长链非编码 RNA MEG3 的下调通过上调 TGF-β1 促进人肝癌细胞的增殖、迁移和侵袭。

Downregulation of long non-coding RNA MEG3 promotes proliferation, migration, and invasion of human hepatocellular carcinoma cells by upregulating TGF-β1.

机构信息

Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China.

Department of Stomatology, Qingdao Municipal Hospital, Qingdao, China.

出版信息

Acta Biochim Biophys Sin (Shanghai). 2019 Jun 20;51(6):645-652. doi: 10.1093/abbs/gmz046.

DOI:10.1093/abbs/gmz046
PMID:31089680
Abstract

Hepatocellular carcinoma is a common malignant cancer with high incidence. And long non-coding RNAs (lncRNAs) play pivotal roles in the development of different types of cancers. In this study, we aimed to investigate the role of lncRNA maternally expressed gene 3 (MEG3) in the development and progression of hepatocellular carcinoma. Expression of MEG3 in tumor tissues and adjacent healthy tissues of hepatocellular carcinoma patients, as well as the serum of both hepatocellular carcinoma patients and healthy controls, was detected by quantitative reverse transcriptase-polymerase chain reaction. The results showed that expression level of MEG3 was significantly lower in tumor tissues than in adjacent healthy tissues. Serum level of MEG3 was also significantly lower in hepatocellular carcinoma patients than in normal controls. The receiver operating characteristic curve analysis was used to evaluate the diagnostic value of MEG3 for hepatocellular carcinoma, and the prognostic value of MEG3 for this disease was analyzed using Kaplan-Meier method. The results indicated that serum level of MEG3 was a diagnostic and prognostic marker for hepatocellular carcinoma. We also found that MEG3 small interfering Ribonucleic Acid (siRNA) silencing promoted the proliferation, migration, and invasion of hepatocellular carcinoma cells by CCK-8 assay, transwell migration, and invasion assay, respectively, while TGF-β inhibitor treatment reduced those enhancing effects. MEG3 siRNA silencing also increased the expression level of TGF-β1. These results indicated that downregulation of MEG3 can promote proliferation, migration, and invasion of human hepatocellular carcinoma cells by upregulating TGF-β1 expression.

摘要

肝细胞癌是一种常见的恶性癌症,发病率较高。长链非编码 RNA(lncRNA)在不同类型癌症的发展中起着关键作用。在这项研究中,我们旨在研究 lncRNA 母系表达基因 3(MEG3)在肝细胞癌发展和进展中的作用。通过定量逆转录-聚合酶链反应检测肝细胞癌患者肿瘤组织和相邻正常组织以及肝细胞癌患者和健康对照者血清中的 MEG3 表达。结果表明,MEG3 在肿瘤组织中的表达水平明显低于相邻的正常组织。肝细胞癌患者血清中的 MEG3 水平也明显低于正常对照组。使用受试者工作特征曲线分析评估 MEG3 对肝细胞癌的诊断价值,并使用 Kaplan-Meier 方法分析 MEG3 对该疾病的预后价值。结果表明,血清 MEG3 水平是肝细胞癌的诊断和预后标志物。我们还发现,MEG3 小干扰核糖核酸(siRNA)沉默通过 CCK-8 测定、Transwell 迁移和侵袭测定分别促进了肝细胞癌细胞的增殖、迁移和侵袭,而 TGF-β 抑制剂处理降低了这些增强作用。MEG3 siRNA 沉默还增加了 TGF-β1 的表达水平。这些结果表明,下调 MEG3 通过上调 TGF-β1 表达可以促进人肝细胞癌细胞的增殖、迁移和侵袭。

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