Ubiquitination, a crucial post-translational modification, controls substrate degradation and can be reversed by deubiquitinases (DUBs). An increasing number of studies are showing that DUBs regulate the malignant behavior and chemotherapy resistance of gastric cancer (GC) by stabilizing various proteins. However, the expression level and biological function of the DUB, proteasome 26S subunit, non-ATPase 7 (PSMD7), in GC remains unknown. Herein, we report for the first time that PSMD7 is frequently overexpressed in GC tissues. Elevated levels of PSMD7 were also detected in GC cell lines. Notably, the upregulation of PSMD7 closely correlated with malignant clinical parameters and reduced the survival of GC patients. Functionally, we found that PSMD7 knockdown consistently suppressed the proliferation, migration, and invasion of AGS and SGC-7901 cells. Ectopic expression of PSMD7 facilitated GC cell proliferation and mobility. Based on protein-protein interaction prediction, RAD23 homolog B (RAD23B) protein was identified as a candidate substrate of PSMD7. PSMD7 positively regulated the abundance of RAD23B and xeroderma pigmentosum, complementation group C (XPC) protein in GC cells. The interaction between PSMD7 and RAD23B was confirmed using protein immunoprecipitation. PSMD7 knockdown enhanced the ubiquitination and degradation of RAD23B protein in GC cells. PSMD7 promoted cell viability, apoptosis resistance, and DNA damage repair in GC cells upon cisplatin (DDP) treatment. Moreover, PSMD7 silencing inhibited tumor growth and enhanced the sensitivity of GC cells to DDP treatment in mice. In summary, PSMD7 was highly expressed in GC and contributed to the malignant behavior and DDP resistance of tumor cells by stabilizing RAD23B.

中文翻译：

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去泛素酶PSMD7通过稳定RAD23B促进胃癌细胞的增殖、侵袭和顺铂耐药

泛素化是一种重要的翻译后修饰，可控制底物降解，并可被去泛素化酶 (DUB) 逆转。越来越多的研究表明，DUBs 通过稳定各种蛋白质来调节胃癌 (GC) 的恶性行为和化疗耐药性。然而，DUB、蛋白酶体 26S 亚基、非 ATPase 7 (PSMD7) 在 GC 中的表达水平和生物学功能仍然未知。在这里，我们首次报道 PSMD7 在 GC 组织中经常过度表达。在 GC 细胞系中也检测到 PSMD7 水平升高。值得注意的是，PSMD7 的上调与恶性临床参数密切相关，并降低了 GC 患者的存活率。在功能上，我们发现 PSMD7 敲低持续抑制增殖、迁移、和 AGS 和 SGC-7901 细胞的侵袭。PSMD7 的异位表达促进了 GC 细胞增殖和迁移。基于蛋白质-蛋白质相互作用预测，RAD23 同源物 B (RAD23B) 蛋白被鉴定为 PSMD7 的候选底物。PSMD7 正向调节 GC 细胞中 RAD23B 和色素性干皮病、互补组 C (XPC) 蛋白的丰度。PSMD7 和 RAD23B 之间的相互作用通过蛋白质免疫沉淀得到证实。PSMD7 敲低增强了 GC 细胞中 RAD23B 蛋白的泛素化和降解。PSMD7 在顺铂 (DDP) 处理后促进 GC 细胞中的细胞活力、细胞凋亡抗性和 DNA 损伤修复。此外，PSMD7 沉默抑制了小鼠的肿瘤生长并增强了 GC 细胞对 DDP 治疗的敏感性。总之，