Musashi1 regulates survival of hepatoma cell lines by activation of Wnt signalling pathway

作者：Chen Kunlun; Gao Qing; Zhang Wei; Liu Zhongwei; Cai Jiangyi; Liu Ying; Xu Jinkai; Li Jie; Yang Yi; Xu Xin^*

来源：Liver International, 2015, 35(3): 986-998.

DOI：10.1111/liv.12458

• cell growth
• hepatoma
• MSI1
• Wnt signalling pathway

Background & AimsMusashi1 (MSI1) belongs to the RNA-binding protein (RBP) family, with functions as translational activator or suppressor of specifically bound mRNA. However, its function in hepatocellular carcinoma (HCC) has been deeply unexplored. Here, we investigated the role of MSI1 for proliferation and tumourigenesis in HCC.
MethodsThe expression of MSI1 in HCC tissues was examined by immunohistochemistry and western blotting. The effects of MSI1 overexpression and silencing on cell proliferation, cell viability, tumoursphere and tumour formation of HCC were explored.
ResultsIn this study, we initially reported that MSI1 was upregulated in HCC. Overexpression of MSI1 in HepG2 cell lines resulted in significantly promoted cell growth, tumour formation and cell cycle progression. Consistently, knockdown of MSI1 in Huh7 cell lines remarkably inhibited cell growth and tumour formation, and caused cell cycle arrest at the G1/S transition. Dual-luciferase assays indicated that MSI1 activated Wnt signal pathway, and APC and DKK1 were direct targets of MSI1.
ConclusionTaken together, these findings indicate that an oncogenic role of MSI1 in HCC may be through modulation of cell growth and cell cycle by activating Wnt pathway via direct downregulation of APC and DKK1.

• 出版日期2015-3
• 单位西安交通大学