1. A Long Noncoding RNA Activated by TGF-β Promotes the Invasion-Metastasis Cascade in Hepatocellular Carcinoma
- Author
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Yingjun Guo, Shuhan Sun, Qi-fei Tao, Shao-bing Wang, Ji-hang Yuan, Yu-zhao Wang, Ning Yang, Weiping Zhou, Tian-tian Wang, Fang Wang, Chuan-chuan Zhou, Guang-Shun Yang, Yuan Yang, Feng Liu, Fu Yang, Jin-zhao Ma, and Wei Pan
- Subjects
Male ,STAT3 Transcription Factor ,Cancer Research ,Carcinoma, Hepatocellular ,Epithelial-Mesenchymal Transition ,Transplantation, Heterologous ,Mice, Nude ,Biology ,Mice ,Downregulation and upregulation ,Transforming Growth Factor beta ,Tumor Cells, Cultured ,Carcinoma ,medicine ,Animals ,Humans ,Neoplasm Invasiveness ,RNA, Messenger ,Neoplasm Metastasis ,Autocrine signalling ,Zinc Finger E-box Binding Homeobox 2 ,Homeodomain Proteins ,Mice, Inbred BALB C ,Gene Expression Profiling ,Liver Neoplasms ,Zinc Finger E-box-Binding Homeobox 1 ,Cell Biology ,Interleukin-11 ,Prognosis ,medicine.disease ,Long non-coding RNA ,Up-Regulation ,Repressor Proteins ,Transplantation ,MicroRNAs ,Oncology ,Hepatocellular carcinoma ,Immunology ,Cancer cell ,Cancer research ,RNA, Long Noncoding ,Neoplasm Transplantation ,Transcription Factors ,Transforming growth factor - Abstract
SummaryThe 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.
- Published
- 2014