Significance of the E3 ubiquitin protein UBR5 as an oncogene and a prognostic biomarker in colorectal cancer.
Significance of the E3 ubiquitin protein UBR5 as an oncogene and a prognostic biomarker in colorectal cancer.
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E3 泛素蛋白 UBR5 作为结直肠癌癌基因和预后生物标志物的意义
DOI：
10.18632/oncotarget.22531
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发表时间：
2017-12-08
期刊：
影响因子：
--
通讯作者：
Chang W
中科院分区：
文献类型：
--
作者：
Xie Z;Liang H;Wang J;Xu X;Zhu Y;Guo A;Shen X;Cao F;Chang W
E3泛素蛋白UBR 5参与多种生物学功能的调节，最近已成为癌症中泛素-蛋白酶体系统（UPS）的关键调节因子。然而，UBR 5在结直肠癌（CRC）中的临床意义和生物学功能知之甚少。在这项研究中，我们比较了UBR 5在结直肠癌和癌旁正常组织中的表达模式，发现UBR 5在结直肠癌中的表达经常升高，可能是通过染色体获得。通过对三个CRC患者队列的研究，我们发现具有高UBR 5 mRNA水平、UBR 5基因扩增或高核UBR 5蛋白水平的患者的预后较差。多因素分析显示，UBR 5的改变是大肠癌预后的独立预测因素，TNM分期是混杂因素。此外，在细胞培养模型中，UBR 5的敲低阻止了CRC细胞的增殖、集落形成、迁移和侵袭。体内动物模型进一步证实，UBR 5敲低降低了CRC肿瘤的生长。总之，我们的研究是第一个系统地研究UBR 5的临床和生物学意义，并得出结论，UBR 5水平升高发挥致癌作用，可能是一个潜在的预后标志物在CRC。
The E3 ubiquitin protein UBR5 has been implicated in the regulation of multiple biological functions and has recently emerged as a key regulator of the ubiquitin-proteasome system (UPS) in cancer. However, the clinical significance and biological function of UBR5 in colorectal cancer (CRC) are poorly understood. In this study, we compared the expression pattern of UBR5 between CRC and adjacent normal tissues and found that UBR5 expression was frequently elevated in CRC, possibly through chromosomal gains. Using three CRC patient cohorts, we found that patients with high UBR5 mRNA levels, UBR5 gene amplification, or high nuclear UBR5 protein levels had poor prognoses. Multivariate analysis showed that the alterations in UBR5 were independent predictors of CRC prognosis with the TNM stage as a confounding factor. Furthermore, knockdown of UBR5 prevented the proliferation, colony formation, migration, and invasion of CRC cells in cell culture models. An in vivo animal model further confirmed that UBR5 knockdown reduced the growth of CRC tumors. In conclusion, our study is the first to systematically investigate the clinical and biological significance of UBR5 and to conclude that an elevated UBR5 level plays an oncogenic role and may be a potential prognostic marker in CRC.
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影响因子：
10.3
作者：
Ougolkov, A;Zhang, B;Minamoto, T
通讯作者：
Minamoto, T
影响因子：
168.9
作者：
Cunningham, David;Atkin, Wendy;Starling, Naureen
通讯作者：
Starling, Naureen
影响因子：
3.3
作者：
Hay-Koren A;Caspi M;Zilberberg A;Rosin-Arbesfeld R
通讯作者：
Rosin-Arbesfeld R
影响因子：
64.8
作者：
Rajagopalan, H;Jallepalli, PV;Lengauer, C
通讯作者：
Lengauer, C
DOI：
10.1073/pnas.1610735113
发表时间：
2016-10-04
影响因子：
11.1
作者：
Sanchez, Anthony;De Vivo, Angelo;Kee, Younghoon
通讯作者：
Kee, Younghoon