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UBR5的过表达通过PTEN/PI3K/Akt信号通路促进胆囊癌肿瘤生长。

Overexpression of UBR5 promotes tumor growth in gallbladder cancer via PTEN/PI3K/Akt signal pathway.

作者信息

Zhang Zhen, Zheng Xin, Li Jiaxin, Duan Jutao, Cui Lihua, Yang Lei, Zhang Lanqiu, Zhang Qi, Wang Ximo

机构信息

Department of Gastrointestinal Surgery, Peking University People's Hospital, Beijing, China.

Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Institute of Acute Abdominal Diseases, Tianjin Nankai Hospital, Tianjin, China.

出版信息

J Cell Biochem. 2019 Jul;120(7):11517-11524. doi: 10.1002/jcb.28431. Epub 2019 Feb 18.

Abstract

As a key regulator of the ubiquitin-proteasome system, ubiquitin protein ligase E3 component N-recognin 5 (UBR5) plays an important role in various cancers. In this study, our results showed for the first time that UBR5 was overexpressed in gallbladder cancer (GBC) tumor tissues. UBR5 overexpression was significantly associated with tumor size, histological and tumor differentiation. UBR5 overexpression was also associated with poor prognosis in patients with GBC. The knockdown of UBR5 remarkably inhibited the cell proliferation and colony formation of GBC-Shandong (SD) cells in vitro and in vivo. UBR5 potentially increases the level of protein kinase B phosphorylation via the degradation of phosphatase and tensin homolog, which contributes to tumor growth in GBC. UBR5 may be an important biomarker for predicting the prognosis of patients with GBC.

摘要

作为泛素-蛋白酶体系统的关键调节因子,泛素蛋白连接酶E3组分N-识别蛋白5(UBR5)在各种癌症中发挥重要作用。在本研究中,我们的结果首次表明UBR5在胆囊癌(GBC)肿瘤组织中过表达。UBR5过表达与肿瘤大小、组织学和肿瘤分化显著相关。UBR5过表达还与GBC患者的不良预后相关。敲低UBR5在体外和体内均显著抑制GBC-山东(SD)细胞的增殖和集落形成。UBR5可能通过降解磷酸酶和张力蛋白同源物来提高蛋白激酶B的磷酸化水平,这有助于GBC中的肿瘤生长。UBR5可能是预测GBC患者预后的重要生物标志物。

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