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

• Published in: BMC cancer Vol. 12; no. 1; p. 227
• Main Authors: Wang, Jian, Li, Jingwu, Shen, Junling, Wang, Chen, Yang, Lili, Zhang, Xinwei
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 08.06.2012; BioMed Central; BMC
• Subjects: Abdomen; Adult; Aged; Analysis; Binding sites; Cancer; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Cell Line, Tumor; Chemotherapy; Development and progression; Down-Regulation; Female; Genetic regulation; Hepatocellular carcinoma; Hepatoma; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Liver - chemistry; Liver - metabolism; Liver cancer; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Male; Metastasis; Metastasis suppressor 1; Microfilament Proteins - genetics; Microfilament Proteins - metabolism; MicroRNA; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; miR-182; Neoplasm Metastasis - genetics; Neoplasm Metastasis - physiopathology; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Physiological aspects; Proportional Hazards Models; Proteins; Real-Time Polymerase Chain Reaction; Tumors
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/1471-2407-12-227

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.