文章：

PSMD12与CDKN3相互作用并促进胰腺癌进展

PSMD12 interacts with CDKN3 and facilitates pancreatic cancer progression 

原文发布日期：2023-04-10 

英文摘要：

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. 

摘要翻译： 

26S蛋白酶体非ATP酶调节亚基12（PSMD12）基因已被证实与多种恶性肿瘤相关，但该基因在胰腺癌（PC）中的作用尚不明确。生物信息学分析显示PSMD12在胰腺癌患者中高表达，且与较短的总生存期相关。PSMD12在胰腺癌组织和细胞系中也呈现高表达现象。上调PSMD12可增强细胞活力、提高克隆形成率并上调PCNA和c-Myc蛋白水平，而抑制PSMD12则能降低这些指标。敲低PSMD12可促进细胞凋亡。裸鼠异种移植瘤实验证实PSMD12在体内能促进胰腺癌肿瘤生长。蛋白质相互作用网络和功能富集分析提示PSMD12可能与细胞周期蛋白依赖性激酶抑制因子3（CDKN3）存在关联。免疫共沉淀和蛋白质印迹实验证实PSMD12能够与CDKN3相互作用并降低其泛素化水平，从而稳定CDKN3蛋白。挽救实验表明PSMD12过表达引发的细胞增殖效应以及敲低诱导的细胞凋亡现象，均可通过调控CDKN3实现逆转。本研究揭示了PSMD12在胰腺癌发展过程中增殖与凋亡调控的关键作用，其可能通过与CDKN3相互作用并降低其泛素化水平来调节CDKN3表达，进而参与胰腺癌的恶性进展。

原文链接：

PSMD12 interacts with CDKN3 and facilitates pancreatic cancer progression