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长链非编码RNA XIST通过充当miR-101的分子海绵来调节EZH2表达,从而调控胃癌进展。

Long non-coding RNA XIST regulates gastric cancer progression by acting as a molecular sponge of miR-101 to modulate EZH2 expression.

作者信息

Chen Dong-Liang, Ju Huai-Qiang, Lu Yun-Xin, Chen Le-Zong, Zeng Zhao-Lei, Zhang Dong-Sheng, Luo Hui-Yan, Wang Feng, Qiu Miao-Zhen, Wang De-Shen, Xu Da-Zhi, Zhou Zhi-Wei, Pelicano Helene, Huang Peng, Xie Dan, Wang Feng-Hua, Li Yu-Hong, Xu Rui-Hua

机构信息

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Medical Oncology, Sun Yat-sen University Cancer Center, No. 651 Dong Feng East Road, Guangzhou, 510060, China.

University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.

出版信息

J Exp Clin Cancer Res. 2016 Sep 13;35(1):142. doi: 10.1186/s13046-016-0420-1.

Abstract

BACKGROUND

Long non-coding RNAs (lncRNAs) have emerged as critical regulators of tumor progression. However, the role and molecular mechanism of lncRNA XIST in gastric cancer is still unknown.

METHODS

Real-time PCR analysis was performed to measure the expression levels of lncRNA XIST in gastric cancer tissues and cell lines, the correlation between lncRNA XIST expression and clinicopathological characteristics and prognosis was analyzed in gastric cancer patients. The biological function of lncRNA XIST on gastric cancer cells were determined both in vitro and in vivo. The regulating relationship between lncRNA XIST and miR-101 was investigated in gastric cancer cells.

RESULTS

lncRNA XIST was significantly up-regulated in gastric cancer tissues and cell lines. Overexpression of lncRNA XIST was markedly associated with larger tumor size, lymph node invasion, distant metastasis and TNM stage in gastric cancer patients. Functionally, knockdown of lncRNA XIST exerted tumor-suppressive effects by inhibiting cell proliferation, migration and invasion in vitro and tumor growth and metastasis in vivo. Furthermore, an inverse relationship between lncRNA XIST and miR-101 was found. Polycomb group protein enhancer of zeste homolog 2 (EZH2), a direct target of miR-101, could mediated the biological effects that lncRNA XIST exerted.

CONCLUSIONS

lncRNA XIST is up-regulated and is associated with aggressive tumor phenotypes and patient survival in gastric cancer, and the newly identified lncRNA XIST/miR-101/EZH2 axis could be a potential biomarkers or therapeutic targets for gastric cancer patients.

摘要

背景

长链非编码RNA(lncRNAs)已成为肿瘤进展的关键调节因子。然而,lncRNA XIST在胃癌中的作用和分子机制仍不清楚。

方法

采用实时PCR分析检测lncRNA XIST在胃癌组织和细胞系中的表达水平,分析lncRNA XIST表达与胃癌患者临床病理特征及预后的相关性。在体外和体内确定lncRNA XIST对胃癌细胞的生物学功能。研究胃癌细胞中lncRNA XIST与miR-101之间的调控关系。

结果

lncRNA XIST在胃癌组织和细胞系中显著上调。lncRNA XIST的过表达与胃癌患者较大的肿瘤大小、淋巴结浸润、远处转移和TNM分期显著相关。在功能上,敲低lncRNA XIST通过抑制体外细胞增殖、迁移和侵袭以及体内肿瘤生长和转移发挥肿瘤抑制作用。此外,发现lncRNA XIST与miR-101呈负相关。miR-101的直接靶标多梳蛋白家族zeste同源物2(EZH2)可介导lncRNA XIST发挥的生物学效应。

结论

lncRNA XIST在胃癌中上调,与侵袭性肿瘤表型和患者生存相关,新发现的lncRNA XIST/miR-101/EZH2轴可能是胃癌患者潜在的生物标志物或治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9217/5020507/817127600ad1/13046_2016_420_Fig1_HTML.jpg

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