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


RESULTS
In 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.


CONCLUSIONS
Taken 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.
Department of General Surgery, Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
Kunlun
K
Chen
Qing
Q
Gao
Wei
W
Zhang
Zhongwei
Z
Liu
Jiangyi
J
Cai
Ying
Y
Liu
Jinkai
J
Xu
Jie
J
Li
Yi
Y
Yang
Xin
X
Xu
D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism*; D000818:Animals; D063646:Carcinogenesis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002453:Cell Cycle; D049109:Cell Proliferation; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway
D025601:Adenomatous Polyposis Coli Protein; C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; C491297:MSI1 protein, human; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins
MSI1; Wnt signalling pathway; cell growth; hepatoma