PSMD4通过抑制内质网应激调控食管癌细胞恶性
蛋白酶体26S亚基非ATPase 4(PSMD4)是重要的蛋白酶体泛素受体,在内质网应激(ERS)中起关键作用。但是,在食道癌(EC)中对PSMD4的研究相对较少。在这里,我们发现PSMD4的表达在EC组织和细胞系中显着增强。细胞计数试剂盒8(CCK-8)分析表明PSMD4的过表达显着增强了Eca109细胞的活力,而抑制PSMD4则降低了Eca109细胞的活力。击倒PSMD4诱导Eca109细胞凋亡和细胞周期停滞。更重要的是,敲低PSMD4可以显着增强葡萄糖调节蛋白78的表达,激活转录因子6和p蛋白激酶R样ER激酶,表明食管癌细胞中ERS反应增强。与对照细胞相比,布雷菲德菌素A显着抑制PSMD4的表达并增加p53上调的细胞凋亡调节剂的表达。但是,在Eca109细胞中过表达PSMD4后,这种作用在很大程度上被逆转,表明沉默PSMD4可以增强ERS诱导的细胞凋亡。总之,PSMD4的上调主要通过减少ERS诱导的细胞凋亡来促进食道癌的进展。**
PSMD4 regulates the malignancy of esophageal cancer cells by suppressing endoplasmic reticulum stress
Proteasome 26S subunit non-ATPase 4 (PSMD4) is an important proteasome ubiquitin receptor and plays a key role in endoplasmic reticulum stress (ERS). However, the study of PSMD4 in esophageal cancer (EC) is relatively rare. Here, we found that the expression of PSMD4 was markedly enhanced in EC tissues and cell lines. The cell counting kit-8 (CCK-8) assay showed that overexpression of PSMD4 significantly enhanced Eca109 cell viability, while inhibition of PSMD4 reduced Eca109 cell viability. Knockdown of PSMD4 induced Eca109 cell apoptosis and cell cycle arrest. More importantly, knockdown of PSMD4 significantly enhanced the expression of glucose regulated protein 78, activating transcription factor 6, and p-protein kinase R-like ER kinase, indicating an enhanced ERS response in esophageal cancer cells. Compared with the control cells, brefeldin A significantly inhibited the expression of PSMD4 and increased the expression of p53-upregulated modulator of apoptosis. However, such effects were largely reversed after overexpressing PSMD4 in Eca109 cells, suggesting that silencing PSMD4 could enhance ERS-induced cell apoptosis. In summary, upregulation of PSMD4 promoted the progression of esophageal cancer mainly by reducing ERS-induced cell apoptosis.
pmid: 31162820 Kaohsiung J Med Sci 影响因子: 1.291 发表日期: 20190604 官网 免费下载
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