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

被引:253
作者
Chen, Dong-liang [1 ]
Ju, Huai-qiang [1 ]
Lu, Yun-xin [1 ]
Chen, Le-zong [1 ]
Zeng, Zhao-lei [1 ]
Zhang, Dong-sheng [1 ]
Luo, Hui-yan [1 ]
Wang, Feng [1 ]
Qiu, Miao-zhen [1 ]
Wang, De-shen [1 ]
Xu, Da-zhi [1 ]
Zhou, Zhi-wei [1 ]
Pelicano, Helene [2 ]
Huang, Peng [2 ]
Xie, Dan [1 ]
Wang, Feng-hua [1 ]
Li, Yu-hong [1 ]
Xu, Rui-hua [1 ]
机构
[1] Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol South China, Collaborat Innovat Ctr Canc Med,Dept Med Oncol, 651 Dong Feng East Rd, Guangzhou 510060, Guangdong, Peoples R China
[2] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA
基金
中国国家自然科学基金;
关键词
Long non-coding RNA; lncRNA XIST; miR-101; EZH2; Gastric cancer; TUMOR PROGRESSION; POOR-PROGNOSIS; INACTIVE-X; POLYCOMB; GENE; PROLIFERATION; MICRORNA-101; CHROMATIN; CELLS; METASTASIS;
D O I
10.1186/s13046-016-0420-1
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
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.
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页数:13
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