Deubiquitinating enzyme USP20 is a positive regulator of Claspin and suppresses the malignant characteristics of gastric cancer cells.
Deubiquitinating enzyme USP20 is a positive regulator of Claspin and suppresses the malignant characteristics of gastric cancer cells.
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去泛素化酶USP20是claspin的正调节因子并抑制胃癌细胞的恶性特征
DOI：
10.3892/ijo.2017.3904
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发表时间：
2017-04
影响因子：
5.2
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Wang C;Yang C;Ji J;Jiang J;Shi M;Cai Q;Yu Y;Zhu Z;Zhang J
本研究旨在探讨USP20在胃癌中的临床意义、生物学功能及机制。应用免疫组织化学方法检测89对原发性胃癌及瘤周胃组织标本中USP20的表达。分析USP20表达与患者生存及临床病理特征的相关性。此外，我们还研究了USP20异位表达的潜在机制及其对GC细胞的影响。我们发现USP20在胃癌组织中的表达相对较低，且与肿瘤大小、肿瘤侵袭程度和TNM分期呈负相关。GC中USP20的高表达预示着更长的生存期。实验发现，小干扰rna介导的USP20表达下调可显著促进细胞增殖，加速G1-S相转变，减弱自噬活性。USP20过表达导致细胞增殖抑制、G1-S细胞周期转换延迟和自噬激活。在机制上，我们证实了在GC细胞中沉默USP20的表达可以降低Claspin蛋白水平而不改变Claspin mRNA水平，这与USP20的抗肿瘤活性有关。此外，Claspin在肿瘤周围组织中的表达水平相对高于胃癌组织，Claspin在胃癌组织中的高表达也与患者预后良好相关。鉴于USP20在胃肿瘤发生和发展中的关键作用，USP20在胃癌中发挥抑瘤作用，有望成为胃癌的治疗靶点。
The aim of the present study was to investigate the clinical significance, the biological function and the mechanisms of USP20 in gastric cancer. The expression of USP20 in 89 pairs of primary gastric cancer and peritumoral gastric tissues specimens were measured by immunohistochemistry. The correlation of USP20 expression with the survival and the clinicopathological characteristics of patients were analyzed. Moreover, the underlying mechanisms of ectopic USP20 expression and its impact on GC cells were also investigated. We found that the expression of USP20 is relatively low in GC tissues and negatively correlated with tumor size, tumor invasion and TNM staging. High expression of USP20 in GC predicted longer survival. Experimentally, small interfering RNA-mediated knockdown of USP20 expression significantly promoted cell proliferation, accelerated G1-S phase transition and attenuated the autophagy activity. Overexpression of USP20 led to the inhibition of proliferation, G1-S cell cycle transition delay and autophagy activation. Mechanistically, we confirmed that silencing the expression of USP20 in GC cells could reduce Claspin protein levels without altering Claspin mRNA levels, which is involved in the antitumor activity of USP20. Furthermore, the expression level of Claspin was relatively higher in peritumoral tissue than that of GC tissues and higher expression of Claspin in GC was also correlated with good prognosis of patients. Given its pivotal role in gastric tumorigenesis and progression, USP20 functioned as the tumor suppressor in GC and possessed promising value to be a therapeutic target for GC.