Shi Ke, Zhang Jin-Zhong, Zhao Rui-Li, Yang Liang, Guo Dan
Department of Biochemistry and Molecular Biology Henan Medical College China.
Editorial Department of Journal of Henan University of Technology Henan University of Technology Zhengzhou China.
FEBS Open Bio. 2018 Mar 7;8(4):533-543. doi: 10.1002/2211-5463.12394. eCollection 2018 Apr.
PSMD7, a 19S proteasome subunit, is overexpressed in most carcinoma cells. It forms a dimer with PSMD14 that functions in the removal of attached ubiquitin chain. However, there is little knowledge about the cellular mechanism of PSMD7 and its exact biological function, especially in cancer cells. In this study, we explored the role of PSMD7 in proliferation, cell cycle, apoptosis, and proteasomal proteolysis in the esophageal squamous cell carcinoma (ESCC) cell line EC9706. Our results showed that PSMD7 was highly expressed in ESCC cells. Downregulation of PSMD7 by lentivirus-mediated shRNA led to decreased proliferation, increased cell apoptosis, and reduced proteasomal function. Notably, lower expression level of mTOR and p70S6K and suppressed activity of mTOR/p70S6K pathway were detected after PSMD7 downregulation. By contrast, increased expression of p-mTOR and p-p70S6K was discovered upon PSMD7 overexpression in Het-1A cells. Furthermore, PSMD7 downregulation contributed to decelerated tumor growth, inhibition of proteasomal function, induced cell apoptosis and attenuated activity of mTOR/p70S6K pathway . These findings suggest that PSMD7 and the mTOR/p70S6K pathway may be a promising candidate for developing therapies for ESCC.
PSMD7是一种19S蛋白酶体亚基，在大多数癌细胞中过表达。它与PSMD14形成二聚体，在去除附着的泛素链中发挥作用。然而，关于PSMD7的细胞机制及其确切生物学功能，尤其是在癌细胞中的功能，人们了解甚少。在本研究中，我们探讨了PSMD7在食管鳞状细胞癌（ESCC）细胞系EC9706的增殖、细胞周期、凋亡和蛋白酶体蛋白水解中的作用。我们的结果表明，PSMD7在ESCC细胞中高表达。慢病毒介导的shRNA下调PSMD7导致增殖减少、细胞凋亡增加和蛋白酶体功能降低。值得注意的是，下调PSMD7后检测到mTOR和p70S6K的表达水平降低以及mTOR/p70S6K通路的活性受到抑制。相比之下，在Het-1A细胞中过表达PSMD7后发现p-mTOR和p-p70S6K的表达增加。此外，下调PSMD7导致肿瘤生长减速、蛋白酶体功能抑制、诱导细胞凋亡以及减弱mTOR/p70S6K通路的活性。这些发现表明，PSMD7和mTOR/p70S6K通路可能是开发ESCC治疗方法的一个有前景的候选靶点。
