蛋白酶体26S亚基，非ATP酶12(PSMD12)基因已被认为与多种恶性肿瘤有关，但在胰腺癌（PC）中的作用尚不清楚。生物信息学分析表明，PSMD12在PC患者中高度表达，并与较短的总体生存期相关。PSMD12还在PC组织和细胞系中表达高水平。上调的PSMD12表现出增强的细胞活力，增加的集落数量以及PCNA和c-Myc的上调水平，而PSMD12的抑制则减弱这些水平。PSMD12敲降促进了细胞凋亡。裸鼠异种移植实验证实了PSMD12在体内促进PC肿瘤生长。蛋白质-蛋白质相互作用网络和功能富集分析表明，PSMD12可能与依赖于周期蛋白依赖激酶抑制剂3(CDKN3)有关。共免疫沉淀和西方印迹结果证实，PSMD12可以相互作用并降低CDKN3的泛素化水平，从而稳定CDKN3蛋白质。救护实验表明，PSMD12过表达导致细胞增殖，而CDKN3调节可以逆转敲降引起的细胞凋亡。该研究揭示了PSMD12在PC发展的增殖和凋亡中的重要作用。PSMD12可能通过与CDKN3相互作用并减弱其泛素化水平来调节CDKN3的表达，并因此参与PC的恶性行为。©2023作者，独家授权给Springer Nature America，Inc。

Proteasome 26S subunit, non-ATPase 12 (PSMD12) genes have been implicated in several types of malignancies but the role of PSMD12 in pancreatic cancer (PC) remains elusive. Bioinformatics analysis showed that PSMD12 was highly expressed in PC patients and was associated with shorter overall survival. PSMD12 was also shown to be highly expressed in PC tissues and cell lines. Upregulated PSMD12 showed enhanced cell viability, increased colony formation rate and upregulated levels of PCNA and c-Myc, while the inhibition of PSMD12 abated these levels. PSMD12 knockdown promoted cell apoptosis. The results of xenografts in nude mice confirmed that PSMD12 promoted PC tumor growth in vivo. Protein‒protein interaction network and functional enrichment analyses implied that PSMD12 may have a connection with cyclin-dependent kinase inhibitor 3 (CDKN3). Co‑immunoprecipitation and western blot results confirmed that PSMD12 could interact with and abate the ubiquitination level of CDKN3, thus stabilizing the CDKN3 protein. Rescue assays showed that PSMD12 overexpression caused cell proliferation and that knockdown-induced cell apoptosis could be reversed by CDKN3 regulation. This work reveals the essential roles of PSMD12 in the proliferation and apoptosis of PC development. PSMD12 may regulate CDKN3 expression by interacting with and abating the ubiquitination level of CDKN3, thereby participating in the malignant behavior of PC.© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.