Luo Changjiang, Yao Yunyi, Yu Zeyuan, Zhou Huinian, Guo Lingyun, Zhang Junqiang, Cao Hongtai, Zhang Genyuan, Li Yumin, Jiao Zuoyi
Department of General Surgery, Lanzhou University Second Hospital and Key Laboratory of Digestive System Tumors of Gansu Province, Lanzhou, Gansu 730030, China.
Department of Medical Technology and Key Laboratory of Biotechnology for Laboratory Medicine of Suzhou, Suzhou Vocational Health College, Suzhou, Jiangsu, 215009, China.
Oncotarget. 2017 May 16;8(20):32639-32654. doi: 10.18632/oncotarget.15947.
Ubiquitin-conjugating enzymes (E2 enzymes) such as UBE2T target proteins for degradation via the proteasome. Here, we examined the effects of UBE2T on the progression of gastric cancer. UBE2T was highly expressed in gastric tumors and gastric cancer cells. siRNA-mediated suppression of UBE2T inhibited gastric cancer cell proliferation and colony formation by promoting cell cycle arrest at G2/M phase and increasing apoptosis. Suppression of UBE2T also attenuated the invasive and metastatic abilities of gastric cancer cells by altering expression of epithelial-mesenchymal transition (EMT)-related factors. A xenograft model in which nude mice were injected with UBE2T knockdown human gastric cancer cells confirmed that suppression of UBE2T also decreased tumor formation and growth in vivo. Expression levels of CCND1, Phospho-GSK3B, WNT family members, and MYC were all affected by UBE2T knockdown. These results suggest that UBE2T plays a critical role in gastric cancer, and that it may serve as a useful prognostic biomarker and therapeutic target in gastric cancer patients.
泛素结合酶(E2酶)如UBE2T通过蛋白酶体靶向蛋白质进行降解。在此,我们研究了UBE2T对胃癌进展的影响。UBE2T在胃肿瘤和胃癌细胞中高表达。siRNA介导的UBE2T抑制通过促进细胞周期阻滞在G2/M期和增加细胞凋亡来抑制胃癌细胞增殖和集落形成。UBE2T的抑制还通过改变上皮-间质转化(EMT)相关因子的表达来减弱胃癌细胞的侵袭和转移能力。将UBE2T敲低的人胃癌细胞注射到裸鼠中的异种移植模型证实,UBE2T的抑制在体内也减少了肿瘤形成和生长。CCND1、磷酸化GSK3B、WNT家族成员和MYC的表达水平均受UBE2T敲低的影响。这些结果表明,UBE2T在胃癌中起关键作用,并且它可能作为胃癌患者有用的预后生物标志物和治疗靶点。