A Long Noncoding RNA Activated by TGF-beta Promotes the Invasion-Metastasis Cascade in Hepatocellular Carcinoma

作者：Yuan, Ji-hang; Yang, Fu; Wang, Fang; Ma, Jin-zhao; Guo, Ying-jun; Tao, Qi-fei; Liu, Feng; Pan, Wei; Wang, Tian-tian; Zhou, Chuan-chuan; Wang, Shao-bing; Wang, Yu-zhao; Yang, Yuan; Yang, Ning; Zhou, Wei-ping; Yang, Guang-shun; Sun, Shu-han^*

来源：Cancer Cell, 2014, 25(5): 666-681.

DOI：10.1016/j.ccr.2014.03.010

• EPITHELIAL-MESENCHYMAL TRANSITION
• GROWTH-FACTOR-BETA
• VENOUS METASTASES
• CANCER METASTASIS
• TUMOR-SUPPRESSOR
• MIR-200 FAMILY
• REPRESSION
• CELLS
• TUMORIGENESIS
• EXPRESSION

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.

• 出版日期2014-5-12
• 单位中国人民解放军第二军医大学