Department of Medical Genetics, Second Military Medical University, Shanghai, 200433, China.
The Third Department of Hepatic Surgery, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai, 200433, China.
Cancer Cell. 2014 May 12;25(5):666-81. doi: 10.1016/j.ccr.2014.03.010. Epub 2014 Apr 24.
The role of TGF-β-induced epithelial-mesenchymal transition (EMT) in cancer cell dissemination is well established, but the involvement of lncRNAs in TGF-β signaling is still unknown. In this study, we observed that the lncRNA-activated by TGF-β (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-β signaling, could predispose HCC patients to metastases and may serve as a potential target for antimetastatic therapies.
TGF-β 诱导的上皮-间充质转化（EMT）在癌细胞扩散中的作用已得到充分证实，但 lncRNA 在 TGF-β 信号中的参与仍不清楚。在这项研究中，我们观察到 TGF-β 激活的 lncRNA（lncRNA-ATB）在肝癌（HCC）转移中上调，并与预后不良相关。lncRNA-ATB 通过竞争性结合 miR-200 家族而上调 ZEB1 和 ZEB2，然后诱导 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 信号来促进播散肿瘤细胞的器官定植。总体而言，lncRNA-ATB 促进了侵袭转移级联反应。因此，这些发现表明，lncRNA-ATB 作为 TGF-β 信号的介质，可能使 HCC 患者易发生转移，并可能成为抗转移治疗的潜在靶点。
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