Caveolin-1 (Cav-1) is a critical structural protein of caveolae and plays an oncogene-like role by participating in abnormal protein glycosylation in hepatocellular carcinoma (HCC). However, the mechanism by which Cav-1 regulates glycosylation and glycosyltransferase expression has not been completely defined. Here, we show that Cav-1 promotes the expression of Rfng, which is a β-1,3-N-acetylglucosaminyltransferase included in the Fringe family. In this study, we showed that the mouse HCC cell line, Hepa1–6, with low Rfng transcription and protein levels, lacked Cav-1 expression, whereas strong Rfng expression was found in the mouse HCC cell line Hca-F, with high transcription and protein levels for Cav-1. Subsequently Cav-1 overexpression in Hepa1–6 was found to activate mitogen-activated protein kinase (MAPK) signaling and induce phosphorylation of the transcription factors Hnf4a and Sp1, which bind to the Rfng promoter region to promote its transcription. On the contrary, when knocking down Cav-1 expression in Hca-F, the activity of the MAPK pathway was significantly inhibited, and phosphorylation of Hnf4a, Sp1 and the expression of Rfng were attenuated. These data reveal that Cav-1 promotes phosphorylation of transcription factors Hnf4a and Sp1, which bind to the Rfng promoter region, via the MAPK signaling pathway, to induce the transcription of Rfng. Our current findings provide molecular genetic evidence that Cav-1 plays an important role in regulating glycosyltransferase expression and may participate in the abnormal glycosylation that mediates the invasion and metastasis of HCC.

中文翻译：

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Caveolin-1通过Erk-Jnk-p38信号通路在小鼠肝癌细胞中促进Rfng表达。

Caveolin-1（Cav-1）是小窝的关键结构蛋白，通过参与肝细胞癌（HCC）中异常的蛋白质糖基化而发挥癌基因样作用。但是，Cav-1调节糖基化和糖基转移酶表达的机制尚未完全确定。在这里，我们显示Cav-1促进Rfng的表达，Rfng是Fringe家族中的一种β-1,3-N-乙酰氨基葡萄糖氨基转移酶。在这项研究中，我们显示了具有低Rfng转录和蛋白质水平的小鼠HCC细胞系Hepa1–6缺乏Cav-1表达，而在具有高转录度的小鼠HCC细胞系Hca-F中发现了强Rfng表达和Cav-1的蛋白质水平。Rfng启动子区域可促进其转录。相反，当敲低Hca-F中的Cav-1表达时，MAPK途径的活性被显着抑制，Hnf4a，Sp1的磷酸化和Rfng的表达减弱。这些数据表明，Cav-1通过MAPK信号通路促进与Rfng启动子区域结合的转录因子Hnf4a和Sp1的磷酸化，从而诱导Rfng的转录。我们目前的发现提供了分子遗传学证据，表明Cav-1在调节糖基转移酶表达中起重要作用，并且可能参与介导HCC侵袭和转移的异常糖基化。