长链非编码RNA SNHG20预测肝癌预后不良，并通过调节上皮-间质转化促进细胞侵袭。

Long non-coding RNA SNHG20 predicts a poor prognosis for HCC and promotes cell invasion by regulating the epithelial-to-mesenchymal transition.

作者信息

Liu Jinxia, Lu Cuihua, Xiao Mingbing, Jiang Feng, Qu Lishuai, Ni Runzhou

机构信息

Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, People's Republic of China.

出版信息

Biomed Pharmacother. 2017 May;89:857-863. doi: 10.1016/j.biopha.2017.01.011. Epub 2017 Mar 6.

DOI:10.1016/j.biopha.2017.01.011

PMID:28282787

Abstract

BACKGROUND

Recently, Accumulating evidence indicates that long noncoding RNAs (lncRNAs) have been shown to have critical regulatory roles in human tumor biology and development. However, the expression pattern and biological function of lncRNA small nucleolar RNA host gene 20 (SNHG20) in hepatocellular carcinoma (HCC) remains largely unknown.

METHODS

The expression of SNHG20 in 96 paired HCC tissues and cell lines were detected by quantitative real-time PCR (qRT-PCR) analysis. Kaplan-Meier survival analysis and log-rank test was used to reveal the association between SNHG20 expression and the overall survival time in HCC patients. CCK8 cell proliferation and transwell invasion assays were performed to analyze the cell proliferation and cell invasion ability. QRT-PCR and western-blotting analysis were performed to demonstrate the mRNA levels and protein expression of ZEB1, ZEB2 and relative epithelial-to-mesenchymal transition (EMT) markers (E-cadherin, N-cadherin and Vimentin).

RESULTS

We showed that the expression level of SNHG20 was significantly up-regulated in 96 pairs of HCC tissues and adjacent normal tissues. Higher SNHG20 expression was positively correlated with larger tumor size and advanced TNM stage, and negatively correlated with the over survival (OS) time for HCC patients. In vitro, loss-function assays revealed that knockdown of SNHG20 inhibited cell proliferation and invasion, whereas, gain-of-function promoted cell proliferation and invasion. Furthermore, knockdown of SNHG20 inhibited ZEB1, ZEB2, N-cadherin and Vimentin expression and up-regulated the E-cadherin expression in HCC cells. Mechanistic investigation revealed that SNHG20 could bind to enhancer of zeste homolog 2 (EZH2) and regulated E-cadherin expression.

CONCLUSION

Our results showed that the SNHG20/EZH2/E-cadhein regulator pathway might contribute to the development of novel therapeutic strategies for HCC patients.

摘要

背景

最近，越来越多的证据表明长链非编码RNA（lncRNAs）在人类肿瘤生物学和发展中发挥着关键的调节作用。然而，lncRNA小核仁RNA宿主基因20（SNHG20）在肝细胞癌（HCC）中的表达模式和生物学功能仍 largely 未知。

方法

通过定量实时PCR（qRT-PCR）分析检测96对HCC组织和细胞系中SNHG20的表达。采用Kaplan-Meier生存分析和对数秩检验来揭示SNHG20表达与HCC患者总生存时间之间的关联。进行CCK8细胞增殖和Transwell侵袭试验以分析细胞增殖和细胞侵袭能力。进行qRT-PCR和蛋白质印迹分析以证明ZEB1、ZEB2和相关上皮-间质转化（EMT）标志物（E-钙黏蛋白、N-钙黏蛋白和波形蛋白）的mRNA水平和蛋白质表达。

结果

我们发现96对HCC组织和相邻正常组织中SNHG20的表达水平显著上调。较高的SNHG20表达与较大的肿瘤大小和晚期TNM分期呈正相关，与HCC患者的总生存（OS）时间呈负相关。在体外，功能缺失试验表明敲低SNHG20可抑制细胞增殖和侵袭，而功能获得则促进细胞增殖和侵袭。此外，敲低SNHG20可抑制HCC细胞中ZEB1、ZEB2、N-钙黏蛋白和波形蛋白的表达并上调E-钙黏蛋白的表达。机制研究表明SNHG20可与zeste同源物2（EZH2）增强子结合并调节E-钙黏蛋白的表达。