Long non-coding RNA ATB promotes malignancy of esophageal squamous cell carcinoma by regulating miR-200b/Kindlin-2 axis.
Long non-coding RNA ATB promotes malignancy of esophageal squamous cell carcinoma by regulating miR-200b/Kindlin-2 axis.
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长链非编码RNA ATB通过调控miR-200b/Kindlin-2轴促进食管鳞癌恶变
DOI：
10.1038/cddis.2017.245
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发表时间：
2017-06-22
影响因子：
9
通讯作者：
Yang X
中科院分区：
文献类型：
--
作者：
Li Z;Wu X;Gu L;Shen Q;Luo W;Deng C;Zhou Q;Chen X;Li Y;Lim Z;Wang X;Wang J;Yang X
食管鳞状细胞癌（ESCC）是癌症相关死亡的主要原因之一，尤其是在中国。此外，晚期患者预后极差。然而，长链非编码RNA lnc-ATB的生物学意义及其在ESCC中的潜在作用仍有待研究。在这项研究中，我们探讨了lnc-ATB在ESCC中的作用及其促进其致癌活性的潜在机制。lnc-ATB在ESCC组织和细胞系中的表达高于正常组织和细胞系。lnc-ATB上调可作为ESCC患者的独立预后预测因子。此外，ESCC细胞的功能丧失实验表明，lnc-ATB的敲低抑制了细胞在体外和体内的增殖和迁移。机制研究表明，lnc-ATB通过调节Kindlin-2发挥致癌作用，而lnc-ATB沉默的抗迁移作用因Kindlin-2的异位表达而减弱。进一步分析表明lnc-ATB作为miR-200b和Kindlin-2的分子海绵。miR-200b/Kindlin-2信号失调介导了ESCC中lnc-ATB的致癌活性。我们的研究结果表明，lnc-ATB预测预后不良，可能作为ESCC患者的潜在治疗靶点。
Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer-related death, especially in China. In addition, the prognosis of late stage patients is extremely poor. However, the biological significance of the long non-coding RNA lnc-ATB and its potential role in ESCC remain to be documented. In this study, we investigated the role of lnc-ATB and the underlying mechanism promoting its oncogenic activity in ESCC. Expression of lnc-ATB was higher in ESCC tissues and cell lines than that in normal counterparts. Upregulated lnc-ATB served as an independent prognosis predictor of ESCC patients. Moreover, loss-of-function assays in ESCC cells showed that knockdown of lnc-ATB inhibited cell proliferation and migration both in vitro and in vivo. Mechanistic investigation indicated that lnc-ATB exerted oncogenic activities via regulating Kindlin-2, as the anti-migration role of lnc-ATB silence was attenuated by ectopic expression of Kindlin-2. Further analysis showed that lnc-ATB functions as a molecular sponge for miR-200b and Kindlin-2. Dysregulated miR-200b/Kindlin-2 signaling mediated the oncogenic activity of lnc-ATB in ESCC. Our results suggest that lnc-ATB predicts poor prognosis and may serve as a potential therapeutic target for ESCC patients.
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影响因子：
5
作者：
Ren, Kewei;Li, Yahua;Lu, Huibin;Li, Zongming;Li, Zhen;Wu, Kai;Li, Zhiqin;Han, Xinwei
通讯作者：
Han, Xinwei
影响因子：
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影响因子：
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通讯作者：
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影响因子：
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通讯作者：
Zhang Y
影响因子：
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作者：
Ren, Yuanyuan;Jin, Hongsong;Huang, He
通讯作者：
Huang, He