MicroRNA-378 promotes cell survival, tumor growth, and angiogenesis by targeting SuFu and Fus-1 expression

MicroRNAs are single-stranded RNA of 18-24 nt expressed endogenously that play important roles in cancer development. Here, we show that expression of miR-378 enhances cell survival, reduces caspase-3 activity, and promotes tumor growth and angiogenesis. Proteomic analysis indicates reduced expressi...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2007-12, Vol.104 (51), p.20350-20355
Main Authors: Lee, Daniel Y, Deng, Zhaoqun, Wang, Chia-Hui, Yang, Burton B
Format: Article
Language:English
Subjects:
Animals
B lymphocytes
Base Pairing
Biological Sciences
Cancer
Cell growth
Cell Line
Cell lines
Cell Proliferation
Cell Survival
COS cells
Delta cells
Enzymes
Gene expression
Humans
Mice
Mice, Inbred Strains
MicroRNA
MicroRNAs - genetics
MicroRNAs - pharmacology
MicroRNAs - physiology
Molecular Sequence Data
Neovascularization, Pathologic - genetics
Polymerase chain reaction
Repressor Proteins - antagonists & inhibitors
Repressor Proteins - genetics
Reverse transcriptase polymerase chain reaction
Survival analysis
Transfection
Tumor Suppressor Proteins - antagonists & inhibitors
Tumor Suppressor Proteins - genetics
Tumors
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Summary:MicroRNAs are single-stranded RNA of 18-24 nt expressed endogenously that play important roles in cancer development. Here, we show that expression of miR-378 enhances cell survival, reduces caspase-3 activity, and promotes tumor growth and angiogenesis. Proteomic analysis indicates reduced expression of suppressor of fused (Sufu), a potential target of miR-378, which was confirmed in vitro and in vivo. Expression of a luciferase construct containing the target site in Sufu was repressed when cotransfected with miR-378. Transfection of a Sufu construct reversed the effect of miR-378, suggesting an important role for miR-378 in tumor cell survival. We also discovered that miR-378 targets Fus-1. Expression of luciferase constructs harboring the target sites in Fus-1 was repressed by miR-378. Fus-1 constructs with or without its 3' UTR were also generated. Cotransfection experiments showed that the presence of miR-378 repressed Fus-1 expression. Suppression of Fus-1 expression by siRNA against Fus-1 enhanced cell survival. Transfection of the Fus-1 construct reversed the function of miR-378 in cell survival. Our results suggest that miR-378 transfection enhanced cell survival, tumor growth, and angiogenesis through repression of the expression of two tumor suppressors, Sufu and Fus-1.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0706901104