Downregulated protein O-fucosyl transferase 1 (Pofut1) expression exerts antiproliferative and antiadhesive effects on hepatocytes by inhibiting Notch signalling

下调蛋白质 O-岩藻糖基转移酶 1 (Pofut1) 表达通过抑制 Notch 信号传导对肝细胞发挥抗增殖和抗粘附作用

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作者:Max Efui Annani-Akollor, Shujing Wang, Jianhui Fan, Linhua Liu, Arshad Ahmed Padhiar, Jianing Zhang

Abstract

The Notch signalling pathway is essential for proper cell growth and development. Many factors interact in the cellular context to bring about its effects. Critical to this process is the influence of Pofut1 whose function is to fucosylate Notch receptors and ligands on the cell surface for proper interaction. Of the three liver cell lines, HepG2, SMMC-7721 (hepatoma cell lines) and L-02 (normal fetal liver cell line) were investigated. In the current study, Pofut1 was silenced in L-02 due to its significantly high level of expression, (P<0.05) using transient SiRNA. Notch1, Cyclin D1 and p53 were significantly suppressed consequently. The effect on cell cycle, proliferation, adhesion and migration were investigated. Evidence adduced, indicate a general modification of cellular function. While proliferation and adhesion were significantly inhibited, the cell cycle arrest was obvious (P<0.05), migration was not affected. The effects seen are akin to those reported in previous studies in hepatoma cells mimicking some of the effects of notch1 silencing. Results of this study indicate a possible role of Pofut1 conferring a tumor suppressor role through the Notch signalling pathway.

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