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KMID : 0381120230450111433
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Genes and Genomics
2023 Volume.45 No. 11 p.1433 ~ p.1443
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ETV4 facilitates proliferation, migration, and invasion of liver cancer by mediating TGF-β signal transduction through activation of B3GNT3
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Zhongcheng Zhou
Bin Wu
Jing Chen
Yiyu Shen
Jing Wang
Xujian Chen
Faming Fei
Liang Li
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Abstract
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Background : Metastasis of liver cancer (LC) is the main cause of its high mortality. ETV4 is a critical regulatory factor in promoting LC progression, but the mechanism that ETV4 impacts LC proliferation, migration, and invasion is poorly understood.
Objective : Investigation of the molecular mechanism of LC metastasis is conducive to developing effective drugs that prevent LC metastasis.
Methods : Expression of ETV4 and its target gene B3GNT3 in LC tissue was analyzed by bioinformatics, and the result was further verified in LC cells by qRT-PCR. In vitro cellular assays evaluated the impact of ETV4 on the proliferation, migration, and invasion of LC cells. Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter gene assay were conducted to analyze the interaction between B3GNT3 and ETV4. SB525334 suppressor was used to treat and access the activation of ETV4 on the TGF-β pathway.
Results : We discovered that ETV4 and B3GNT3 were evidently up-regulated in LC, and high expression of ETV4 was coupled to the increase of proliferation, migration, and invasion of LC cells and epithelial-mesenchymal transition ability. Besides, ETV4 could bind to the B3GNT3 promoter and activate its transcription. Knockdown of B3GNT3 could prominently suppress the effect of up-regulated ETV4 on LC cells. Meanwhile, ETV4 could activate the TGF-β signaling pathway via B3GNT3, while SB525334 treatment notably repressed the functions of ETV4.
Conclusion : ETV4 emerges as a driven oncogene in LC, and the ETV4/B3GNT3-TGF-β pathway promotes proliferation, migration, invasion, and epithelial-mesenchymal transition progress of LC. Inhibition of the pathway may provide an underlying method for the prevention and treatment of LC metastasis.
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KEYWORD
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EVT4, B3GNT3, LC, Proliferation, Migration, Invasion, TGF-β
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