Dataset Information

MicroRNA-199b-5p attenuates TGF-?1-induced epithelial-mesenchymal transition in hepatocellular carcinoma.

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.

Methods

This study aims to investigate the expression status of N-cadherin and its molecular mechanisms in HCC.

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-?1 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-?1-induced Akt phosphorylation, and inhibition of PI3K/Akt pathway blocked TGF-?1-induced N-cadherin overexpression in HCC cells.

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-?1-mediated EMT in HCC cells.

SUBMITTER: Zhou SJ

PROVIDER: S-EPMC5520514 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Publications

MicroRNA-199b-5p attenuates TGF-β1-induced epithelial-mesenchymal transition in hepatocellular carcinoma.

Zhou Shao-Jun SJ Liu Fu-Yao FY Zhang An-Hong AH Liang Hui-Fang HF Wang Ye Y Ma Rong R Jiang Yuan-Hui YH Sun Nian-Feng NF

British journal of cancer 20170606 2

<h4>Background</h4>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.<h4>Methods</h4>This study aims to investigate the expression status of N-cadherin and its molecular mechanisms in HCC.<h4>Results</h4>The expression of N-cadherin was markedly overexpressed in HCC tissues and cell lines. We identified that miR-199b-5p binds to the 3'-U ...[more]

PMID: 28588321

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