In this study, we identified that PSMD7 was overexpressed in BC tissues based on gene expression omnibus (GEO) database and TNMplot web. To investigate the functional role of PSMD7, two BC cell lines, T24 and 5637, were selected. The cells were transfected with vectors containing short hairpin RNAs against PSMD7 or plasmids containing full-length PSMD7 to knockdown or overexpress PSMD7.
Our results revealed that silencing PSMD7 inhibited cell proliferation, cycle progression, migration, invasion, and promoted cell apoptosis, whereas PSMD7 overexpression led to the opposite effects in the BC cells. Mechanically, PSMD7 influenced the protein expression but not the mRNA expression of the Ras-related protein Rab-1 A (RAB1A). PSMD7 combined with RAB1A and negatively regulated its ubiquitination, indicating that PSMD7 enhanced the stability of RAB1A through post-transcriptional modification. Moreover, the rescue experiment demonstrated that RAB1A was an important downstream effector molecule of PSMD7. Besides, the negative regulation of silencing PSMD7 on tumor growth was confirmed in mice.
Our study substantiated a novel mechanism by which PSMD7 stabilized RAB1A to accelerate the progression of BC.
方法:在本研究中,我们根据基因表达综合(GEO)数据库和TNMplot网络确定PSMD7在BC组织中过度表达.为了研究PSMD7的功能作用,两种BC细胞系,选择T24和5637。用含有针对PSMD7的短发夹RNA的载体或含有全长PSMD7的质粒转染细胞以敲低或过表达PSMD7。
结果:我们的结果显示,沉默PSMD7会抑制细胞增殖,周期进展,迁移,入侵,促进细胞凋亡,而PSMD7过表达在BC细胞中导致相反的作用。机械上,PSMD7影响Ras相关蛋白Rab-1A(RAB1A)的蛋白表达,但不影响mRNA表达。PSMD7与RAB1A结合并负调控其泛素化,表明PSMD7通过转录后修饰增强了RAB1A的稳定性。此外,拯救实验表明,RAB1A是PSMD7的重要下游效应分子。此外,在小鼠中证实了沉默PSMD7对肿瘤生长的负调节。
结论:我们的研究证实了PSMD7稳定RAB1A以加速BC进展的新机制。