The ubiquitin–proteasome system (UPS) plays a central role in regulating protein homeostasis in tumor progression. The proteasome subunit Rpn10 is associated with the progression of several tumor types. However, little is known regarding the role of Rpn10 in clear cell renal cell carcinoma (ccRCC). In this study, we found that overexpression of Rpn10 increased ccRCC cell proliferation, migration, and invasion. Silencing Rpn10 expression resulted in decreased cell proli-feration, migration, and invasion in ccRCC cells. Knockdown of Rpn10 inhibits tumor growth and cell proliferation in vivo. Furthermore, we demonstrated that Rpn10 increased cell proliferation, migration, and invasion via regulation of the nuclear factor kappa B (NF-κB) pathway. Rpn10 directly promoted inhibitor of nuclear factor-kappa B alpha (IκBα) degradation through the UPS. Moreover, we observed that upregulation of Rpn10 or downregulation of IκBα in ccRCC was associated with poor prognosis. We found that the combination of these two parameters was a more powerful predictor of poor prognosis than either parameter alone. Collectively, these findings provide evidence that Rpn10 promotes the progression of ccRCC by regulation of the NF-κB pathways and is a prognostic indicator for patients with ccRCC.

中文翻译：

---

Rpn10 上调通过激活 NF-κB 通路促进透明细胞肾细胞癌的肿瘤进展

泛素-蛋白酶体系统 (UPS) 在调节肿瘤进展中的蛋白质稳态方面发挥着核心作用。蛋白酶体亚基 Rpn10 与几种肿瘤类型的进展有关。然而，关于 Rpn10 在透明细胞肾细胞癌 (ccRCC) 中的作用知之甚少。在这项研究中，我们发现 Rpn10 的过表达增加了 ccRCC 细胞的增殖、迁移和侵袭。沉默 Rpn10 表达导致 ccRCC 细胞的细胞增殖、迁移和侵袭减少。敲低 Rpn10 抑制体内肿瘤生长和细胞增殖. 此外，我们证明 Rpn10 通过调节核因子 kappa B (NF-κB) 途径增加细胞增殖、迁移和侵袭。Rpn10 通过 UPS 直接促进核因子-κB α (IκBα) 降解的抑制剂。此外，我们观察到 ccRCC 中 Rpn10 的上调或 IκBα 的下调与不良预后相关。我们发现这两个参数的组合比单独的任何一个参数更能预测不良预后。总的来说，这些发现提供了证据，表明 Rpn10 通过调节 NF-κB 通路促进 ccRCC 的进展，并且是 ccRCC 患者的预后指标。