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

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.

journal_name

Oncol Rep

journal_title

Oncology reports

authors

Zhang Y,Zhang D,Jiang J,Dong L

doi

10.3892/or.2016.5273

subject

Has Abstract

pub_date

2017-01-01 00:00:00

pages

323-332

issue

1

eissn

1021-335X

issn

1791-2431

journal_volume

37

pub_type

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