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Logo of bmccancBioMed Centralsearchsubmit a manuscriptregisterthis articleBMC Cancer
BMC Cancer. 2012; 12: 227.
Published online Jun 8, 2012. doi:  10.1186/1471-2407-12-227
PMCID: PMC3492170
MicroRNA-182 downregulates metastasis suppressor 1 and contributes to metastasis of hepatocellular carcinoma
Jian Wang,corresponding author#1 Jingwu Li,#2,3 Junling Shen,#4 Chen Wang,1 Lili Yang,1 and Xinwei Zhang1
1Department of 4th Abdominal Oncology, Cancer Hospital and Institute of Tianjin Medical University, Tianjin, 300060, China
2Department of Abdominal Oncology, Tangshan People's Hospital, Tangshan, 063001, China
3Hebei Medical University, Shijiazhuang, 050017, China
4Qingdao Agricultural University, Qingdao, 266109, China
corresponding authorCorresponding author.
#Contributed equally.
Jian Wang: jianwang04/at/; Jingwu Li: lijingwu/at/; Junling Shen: junling5541/at/; Chen Wang:; Lili Yang: yanglili2006/at/; Xinwei Zhang: xinweizhang/at/
Received January 12, 2012; Accepted June 1, 2012.
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.
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.
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.
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
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