Loss of miR-638 promotes invasion and epithelial-mesenchymal transition by targeting SOX2 in hepatocellular carcinoma

Zhang,Yu; Zhang,Di; Jiang,Jiong; Dong,Lei

doi:10.3892/or.2016.5273

Loss of miR-638 promotes invasion and epithelial-mesenchymal transition by targeting SOX2 in hepatocellular carcinoma

Authors:
- Yu Zhang
- Di Zhang
- Jiong Jiang
- Lei Dong
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Affiliations: Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China, Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
Published online on: November 23, 2016 https://doi.org/10.3892/or.2016.5273
Pages: 323-332

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Abstract

Aberrant expression of microRNAs has been identified as regulators of biological processes of hepatocellular carcinoma (HCC) by negatively regulating protein-coding mRNAs. Several studies have demonstrated that miR-638 expression was dysregulated in various human cancers. However, the clinical significance and underlying mechanisms of miR-638 involved in HCC remain to be elucidated. Herein, we confirmed that a reduced miR-638 expression was present in HCC tissues and cell lines. Our clinical analysis revealed that the downregulated miR-638 expression was significantly correlated with poor prognostic features including high Edmondson-Steiner grade, venous infiltration and advanced tumor-node-metastasis (TNM) stage. Moreover, we demonstrated that miR-638 was a novel independent prognostic marker for predicting 5-year survival of HCC patients. Functionally, overexpressed miR-638 expression inhibited cell migration and invasion, while downregulated miR-638 reversed the effect. In addition, miR-638 could regulate SOX2 by directly binding to its 3'-UTR. Alternation of SOX2 expression at least partially abolished the migration and invasion effects of miR-638 on HCC cells. Aberrant miR-638 expression could regulate the expression level of epithelial-to-mesenchymal transition markers in vitro and in vivo by modulating SOX2 expression. In conclusion, our data indicated that miR-638 functioned as a tumor suppressor gene and play a critical role in the development of HCC.

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