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Open Access Highly Accessed Research article

MicroRNA-182 downregulates metastasis suppressor 1 and contributes to metastasis of hepatocellular carcinoma

Jian Wang1*, Jingwu Li23, Junling Shen4, Chen Wang1, Lili Yang1 and Xinwei Zhang1

Author Affiliations

1 Department of 4th Abdominal Oncology, Cancer Hospital and Institute of Tianjin Medical University, Tianjin, 300060, China

2 Department of Abdominal Oncology, Tangshan People's Hospital, Tangshan, 063001, China

3 Hebei Medical University, Shijiazhuang, 050017, China

4 Qingdao Agricultural University, Qingdao, 266109, China

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BMC Cancer 2012, 12:227  doi:10.1186/1471-2407-12-227

Published: 8 June 2012

Abstract

Background

miR-182 is one of the most significantly up-regulated miRNAs in hepatocellular carcinoma (HCC). Metastasis suppressor 1 (MTSS1), one target gene of miR-182, plays an important role in the metastasis of cancers. However, it remains unclear what role does function and mechanism of miR-182 and MTSS1play in HCC.

Methods

miR-182 expression was tested in 86 cases of paired HCC and normal tissues by real-time PCR and the relationships between miR-182 expression and clinicopathological parameters were analyzed. The expression of MTSS1 was evaluated by immunohistochemistry and western blot in the above tissues and its correlation with miR-182 expression was analyzed. Moreover, western blot and invasion assays were performed after transfection of pre-miR-182 or anti-miR-182 to HCC cell lines. In addition, luciferase assays was performed to confirm the regulation of miR-182 on MTSS1.

Results

Compared with normal tissue, miR-182 was up-regulated and MTSS1 was down-regulated in HCC tissues. Moreover, the over-expression of miR-182 was correlated with intrahepatic metastasis (p = 0.034) and poor prognosis (p = 0.039) of HCC patients. There was a negative correlation between miR-182 and MTSS1 expression in both HCC tissues (r = −0.673, p < 0.01) and HCC cell lines (r = −0.931, p = 0.021). Furthermore, the up-regulation of miR-182 resulted in the down-regulation of MTSS1 and increased invasive potential of HUH-1, and reverse results were also confirmed when the expression of miR-182 was inhibited. In addition, the results of the luciferase assay demonstrated the targeted regulation of miR-182 on MTSS1.

Conclusions

miR-182 could promote metastasis of HCC and inhibit the expression of MTSS1. miR-182 and MTSS1 are potential prognostic markers and/or therapeutic targets in HCC.

Keywords:
Hepatocellular carcinoma; miR-182; Metastasis suppressor 1; Metastasis