A Long Noncoding RNA Activated by TGF-β Promotes the Invasion-Metastasis Cascade in Hepatocellular Carcinoma
A Long Noncoding RNA Activated by TGF-β Promotes the Invasion-Metastasis Cascade in Hepatocellular Carcinoma
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TGF-β激活的长非编码RNA促进肝细胞癌的侵袭转移级联反应
DOI：
10.1016/j.ccr.2014.03.010
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发表时间：
2014-05-12
期刊：
影响因子：
50.3
通讯作者：
Sun, Shu-han
中科院分区：
文献类型：
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作者：
Yuan, Ji-hang;Yang, Fu;Sun, Shu-han
转化生长因子-β诱导的上皮-间充质转化(EMT)在癌细胞扩散中的作用已被证实，但lncRNAs在转化生长因子-β信号转导中的作用尚不清楚。在本研究中，我们观察到由转化生长因子-β激活的lncRNA(lncRNA-ATB)在肝细胞癌转移中表达上调，并与预后不良有关。LncRNA-ATB通过竞争性结合miR-200家族上调ZEB1和ZEB2的表达，从而诱导EMT和侵袭。此外，lncRNA-ATB通过结合IL-11mRNA，自分泌诱导IL-11，并触发STAT3信号，促进了播散性肿瘤细胞的器官定植。在全球范围内，lncRNA-ATB促进侵袭-转移级联反应。因此，这些发现表明，作为转化生长因子-β信号的介导者，lncRNA-ATB可能使肝癌患者易于转移，并可能成为抗转移治疗的潜在靶点。
The role of TGF-beta-induced epithelial-mesenchymal transition (EMT) in cancer cell dissemination is well established, but the involvement of lncRNAs in TGF-beta signaling is still unknown. In this study, we observed that the lncRNA-activated by TGF-beta (lncRNA-ATB) was upregulated in hepatocellular carcinoma (HCC) metastases and associated with poor prognosis. lncRNA-ATB upregulated ZEB1 and ZEB2 by competitively binding the miR-200 family and then induced EMT and invasion. In addition, lncRNA-ATB promoted organ colonization of disseminated tumor cells by binding IL-11 mRNA, autocrine induction of IL-11, and triggering STAT3 signaling. Globally, lncRNA-ATB promotes the invasion-metastasis cascade. Thus, these findings suggest that lncRNA-ATB, a mediator of TGF-beta signaling, could predispose HCC patients to metastases and may serve as a potential target for antimetastatic therapies.