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首页> 外文期刊>FEBS Open Bio >PSMD7 downregulation induces apoptosis and suppresses tumorigenesis of esophageal squamous cell carcinoma via the mTOR/p70S6K pathway
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PSMD7 downregulation induces apoptosis and suppresses tumorigenesis of esophageal squamous cell carcinoma via the mTOR/p70S6K pathway

机译：PSMD7下调通过mTOR / p70S6K途径诱导凋亡并抑制食道鳞状细胞癌的发生

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摘要

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‐mTORSer2448 and p‐p70S6KThr421/Ser424 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 in vivo. These findings suggest that PSMD7 and the mTOR/p70S6K pathway may be a promising candidate for developing therapies for ESCC.
机译：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起作用。但是，关于PSMD7的细胞机制及其确切的生物学功能（特别是在癌细胞中）知之甚少。在这项研究中，我们探讨了PSMD7在食管鳞状细胞癌（ESCC）细胞系EC9706中的增殖，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细胞中高度表达。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，PSMD7下调后，mTOR和p70S6K的表达水平降低，mTOR / p70S6K通路的活性降低。相比之下，在Het-1A细胞中过表达PSMD7后，发现p-mTORSer2448和p-p70S6KThr421 / Ser424的表达增加。此外，PSMD7的下调有助于体内肿瘤生长的减速，蛋白酶体功能的抑制，诱导的细胞凋亡和mTOR / p70S6K通路活性的减弱。这些发现表明PSMD7和mTOR / p70S6K途径可能是开发ESCC治疗的有希望的候选者。

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