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MicroRNA-199b-5p attenuates TGF-β1-induced epithelial-mesenchymal transition in hepatocellular carcinoma.
- Source :
-
British journal of cancer [Br J Cancer] 2017 Jul 11; Vol. 117 (2), pp. 233-244. Date of Electronic Publication: 2017 Jun 06. - Publication Year :
- 2017
-
Abstract
- Background: Accumulating evidence indicates that N-cadherin is a cell adhesion molecule that has critical roles in tumour progression. However, the role of N-cadherin in hepatocellular carcinoma (HCC) remains controversial.<br />Methods: This study aims to investigate the expression status of N-cadherin and its molecular mechanisms in HCC.<br />Results: The expression of N-cadherin was markedly overexpressed in HCC tissues and cell lines. We identified that miR-199b-5p binds to the 3'-UTR of N-cadherin mRNA, thus decreasing N-cadherin expression in HCC cells. We also found the downregulation of miR-199b-5p in HCC specimens, which was inversely correlated with N-cadherin upregulation, predicted poor clinical outcomes in HCC patients. Next, we determined that miR-199b-5p overexpression promoted cell aggregation, suppressed cell migration and invasion in HCC cells, and inhibited xenografts tumour metastasis in nude mice. Moreover, we demonstrated that miR-199b-5p attenuated TGF-β1 induced epithelial-mesenchymal transition (EMT) -associated traits, while its effects could be partially reversed by N-cadherin restoration. Finally, we examined that N-cadherin downregulation or miR-199b-5p overexpression suppressed TGF-β1-induced Akt phosphorylation, and inhibition of PI3K/Akt pathway blocked TGF-β1-induced N-cadherin overexpression in HCC cells.<br />Conclusions: Our data demonstrate that N-Cadherin was markedly overexpressed and miR-199b-5p was significantly downregulated in HCC. MiR-199b-5p exerts inhibitory effects on EMT, and directly targets N-cadherin in HCC, supporting the potential utility of miR-199b-5p as a promising strategy to treat HCC. Also, a positive regulatory loop exists between N-cadherin and Akt signalling represents a novel mechanism of TGF-β1-mediated EMT in HCC cells.
- Subjects :
- Animals
Cadherins genetics
Carcinoma, Hepatocellular pathology
Cell Movement genetics
Epithelial-Mesenchymal Transition genetics
Gene Expression Regulation, Neoplastic
Hep G2 Cells
Humans
Liver Neoplasms pathology
Mice
Signal Transduction
Xenograft Model Antitumor Assays
Cadherins biosynthesis
Carcinoma, Hepatocellular genetics
Liver Neoplasms genetics
MicroRNAs genetics
Transforming Growth Factor beta1 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1532-1827
- Volume :
- 117
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- British journal of cancer
- Publication Type :
- Academic Journal
- Accession number :
- 28588321
- Full Text :
- https://doi.org/10.1038/bjc.2017.164