Cancer cell stemness contributes significantly to intrahepatic cholangiocarcinoma (ICC) progression. However, the roles of deubiquitinating enzymes (DUBs) in ICC modulation are poorly understood. Ubiquitin specific peptidase 10 (USP10) was highly expressed in ICC spheres. The interaction between USP10 and snail family transcriptional repressor 1 (SNAI1) reduced the polyubiquitination of the SNAI1 protein and stabilized the SNAI1 protein. USP10 knockdown in RBE cells inhibited cell proliferation, promoted cell apoptosis and decreased the diameter of the formed spheres and the expression levels of CD44, EpCAM, OCT4 and SOX2. SNAI1 overexpression alleviated the effect of USP10 knockdown in RBE cells. In addition, the knockdown of USP10 attenuated the ability of RBE cells to form tumors subcutaneously in nude mice. Our results revealed that USP10 attenuates ICC cell malignancy by deubiquitinating SNAI1, indicating that USP10 could be developed as a therapeutic target for ICC treatment.

癌细胞干性对肝内胆管癌（ICC）的进展有显着影响。然而，人们对去泛素化酶 (DUB) 在 ICC 调节中的作用知之甚少。泛素特异性肽酶 10 (USP10) 在 ICC 球体中高度表达。USP10 和 snail family 转录阻遏蛋白 1 (SNAI1) 之间的相互作用减少了 SNAI1 蛋白的多泛素化并稳定了 SNAI1 蛋白。RBE细胞中USP10敲低抑制细胞增殖，促进细胞凋亡，降低形成球的直径以及CD44、EpCAM、OCT4和SOX2的表达水平。SNAI1 过表达减轻了 RBE 细胞中 USP10 敲低的影响。此外，USP10的敲低削弱了RBE细胞在裸鼠皮下形成肿瘤的能力。我们的结果显示，USP10 通过去泛素化 SNAI1 来减轻 ICC 细胞的恶性肿瘤，这表明 USP10 可以开发为 ICC 治疗的治疗靶点。