Ubiquitin-specific protease 3 overexpression promotes gastric carcinogenesis and is predictive of poor patient prognosis.

Ubiquitin-specific protease 3 overexpression promotes gastric carcinogenesis and is predictive of poor patient prognosis.
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DOI:
10.1111/cas.13789
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发表时间:
2018-11
期刊:
影响因子:
5.7
通讯作者:
Lin KY
Lin KY
中科院分区:
医学2区
文献类型:
--
作者:
Fang CL;Lin CC;Chen HK;Hseu YC;Hung ST;Sun DP;Uen YH;Lin KY

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尽管胃癌(GC)是最常见的癌症之一,但对其发展和致癌作用的了解有限。迄今为止,泛素特异性蛋白酶 3 (USP3) 在包括 GC 在内的所有类型癌症中的表达仍不清楚。本研究探讨了USP3在胃癌发生和预后中的作用。我们测量了正常组织和胃癌组织和细胞系中的 USP3 表达。评估了USP3蛋白水平与临床病理参数之间的相关性,以及USP3蛋白水平对无病生存的意义。使用小发夹RNA技术和转染来研究USP3操作对细胞增殖和扩散的影响。此外,利用异种移植物增殖和转移来探讨USP3对动物肿瘤生长和转移的影响。在 GC 细胞和组织中观察到 USP3 表达增加。 USP3 的过度表达与多种临床病理参数和较差的无病生存率显着相关。多变量Cox回归分析显示USP3的过度表达是一个独立的预后生物标志物。 USP3 的沉默可抑制 GC 细胞的体外增殖和扩散以及体内异种移植物的增殖和转移;然而,当USP3过表达时,得到相反的结果。进一步的研究表明,USP3 通过调节细胞周期控制和上皮间质转化相关分子来影响细胞增殖和扩散。这项研究表明,USP3 过度表达可以成为预测 GC 患者预后的有用生物标志物,并且 USP3 靶向代表了治疗 GC 的潜在方式。
Although gastric cancer (GC) is one of the most common cancers, knowledge of its development and carcinogenesis is limited. To date, expression of ubiquitin‐specific protease 3 (USP3) in all types of cancer, including GC, is still unknown. The present study explored the involvement of USP3 in the carcinogenesis and prognosis of GC. We measured USP3 expression in normal and GC tissues and cell lines. Correlations between USP3 protein level and clinicopathological parameters, as well as the significance of USP3 protein level for disease‐free survival were assessed. Small hairpin RNA technology and transfection were used to investigate the effect of USP3 manipulation on cell proliferation and spreading. Moreover, xenograft proliferation and metastasis were used to explore the influence of USP3 on tumor growth and metastasis in animals. An increase in USP3 expression was observed in GC cells and tissues. The overexpression of USP3 was significantly correlated with several clinicopathological parameters and poor disease‐free survival. Multivariate Cox regression analysis showed that the overexpression of USP3 was an independent prognostic biomarker. Silencing of USP3 suppressed GC cell proliferation and spreading in vitro as well as xenograft proliferation and metastasis in vivo; however, opposite results were obtained when USP3 was overexpressed. Further studies showed that USP3 influenced cell proliferation and spreading by regulating the cell cycle control‐ and epithelial‐mesenchymal transition‐related molecules. This study suggests that USP3 overexpression can be a useful biomarker for predicting the outcomes of GC patients and that USP3 targeting represents a potential modality for treating GC.
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发表时间: 2017-04
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发表时间: 2009-08-08
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影响因子: --
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