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Musashi1 regulates survival of hepatoma cell lines by activation of Wnt signalling pathway
Author(s) -
Chen Kunlun,
Gao Qing,
Zhang Wei,
Liu Zhongwei,
Cai Jiangyi,
Liu Ying,
Xu Jinkai,
Li Jie,
Yang Yi,
Xu Xin
Publication year - 2015
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.12458
Subject(s) - wnt signaling pathway , downregulation and upregulation , cell growth , cell cycle , cancer research , gene silencing , cell cycle checkpoint , gene knockdown , cell , biology , cell culture , viability assay , signal transduction , microbiology and biotechnology , chemistry , gene , genetics
Background & Aims Musashi1 (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. Methods The expression of MSI 1 in HCC tissues was examined by immunohistochemistry and western blotting. The effects of MSI 1 overexpression and silencing on cell proliferation, cell viability, tumoursphere and tumour formation of HCC were explored. Results In this study, we initially reported that MSI 1 was upregulated in HCC . Overexpression of MSI 1 in HepG2 cell lines resulted in significantly promoted cell growth, tumour formation and cell cycle progression. Consistently, knockdown of MSI 1 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 MSI 1 activated Wnt signal pathway, and APC and DKK 1 were direct targets of MSI 1. Conclusion Taken together, these findings indicate that an oncogenic role of MSI 1 in HCC may be through modulation of cell growth and cell cycle by activating Wnt pathway via direct downregulation of APC and DKK 1.