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A Long Noncoding RNA Activated by TGF-β Promotes the Invasion-Metastasis Cascade in Hepatocellular Carcinoma
- Source :
- Cancer Cell. 25:666-681
- Publication Year :
- 2014
- Publisher :
- Elsevier BV, 2014.
-
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.
- 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
Subjects
Details
- ISSN :
- 15356108
- Volume :
- 25
- Database :
- OpenAIRE
- Journal :
- Cancer Cell
- Accession number :
- edsair.doi.dedup.....9dc2b6cc1e83571b32385eab134176fe