Expression of the F‐box protein FBXO11 has been shown to be down‐regulated in various tumors, but its role in hepatocellular carcinoma (HCC) progression remains unclear. Here, we examined the role of FBXO11 in HCC cell stemness. We report that FBXO11 expression is significantly decreased in HCC cells, and overexpression of FBXO11 decreased the expression of HCC stemness markers, ALDH1 activity and sphere‐forming ability. In addition, overexpression of FBXO11 reduced the migration ability and epithelial‐mesenchymal transition of HCC cells. Mechanistically, overexpression of FBXO11 decreased the protein level, but not mRNA level, of Snail by directly interacting with Snail and promoting Snail degradation through the ubiquitin‐proteasome system. Overexpression of Snail rescued the inhibitory effect of FBXO11 overexpression on HCC cell stemness. This study reveals the existence of a novel FBXO11/Snail regulatory axis that is necessary for HCC cell stemness.

中文翻译：

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F-box 蛋白 FBXO11 通过促进泛素介导的 Snail 降解来抑制肝细胞癌的干性。

F-box 蛋白 FBXO11 的表达已被证明在各种肿瘤中下调，但其在肝细胞癌 (HCC) 进展中的作用仍不清楚。在这里，我们检查了 FBXO11 在 HCC 细胞干性中的作用。我们报告说，FBXO11 表达在 HCC 细胞中显着降低，并且 FBXO11 的过表达降低了 HCC 干性标记物、ALDH1 活性和球体形成能力的表达。此外，FBXO11 的过表达降低了 HCC 细胞的迁移能力和上皮间质转化。从机制上讲，FBXO11 的过表达通过与 Snail 直接相互作用并通过泛素-蛋白酶体系统促进 Snail 降解来降低 Snail 的蛋白质水平，而不是 mRNA 水平。Snail 的过表达挽救了 FBXO11 过表达对 HCC 细胞干性的抑制作用。