Transforming Growth Factor-β-Induced Long Noncoding RNA Promotes Liver Cancer Metastasis via RNA-RNA Crosstalk

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.