Wen Mingxin, Kwon Yongwon, Wang Yongsheng, Mao Jian-Hua, Wei Guangwei
Department of Human Anatomy and Key Laboratory of Experimental Teratology, Ministry of Education, Shandong University School of Medicine, Jinan, Shandong, 250012 P.R. China.
Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94127, USA.
Oncotarget. 2015 Sep 22;6(28):25226-39. doi: 10.18632/oncotarget.4712.
Increased expression of ubiquitin-conjugating enzyme E2T (UBE2T) is reported in human prostate cancer. However, whether UBE2T plays any functional role in prostate cancer development remains unknown. We here report the first functional characterization of UBE2T in prostate carcinogenesis. Prostate cancer tissue array analysis confirmed upregulation of UBE2T in prostate cancer, especially these with distant metastasis. Moreover, higher level of UBE2T expression is associated with poorer prognosis of prostate cancer patients. Ectopic expression of UBE2T significantly promotes prostate cancer cell proliferation, motility and invasion, while UBE2T depletion by shRNA significantly inhibits these abilities of prostate cancer cells. Xenograft mouse model studies showed that overexpression of UBE2T promotes whereas UBE2T depletion inhibits tumor formation and metastasis significantly. Collectively, we identify critical roles of UBE2T in prostate cancer development and progression. These findings may serve as a framework for future investigations designed to more comprehensive determination of UBE2T as a potential therapeutic target.
据报道，泛素结合酶E2T（UBE2T）在人类前列腺癌中的表达增加。然而，UBE2T在前列腺癌发生过程中是否发挥任何功能作用仍不清楚。我们在此报告了UBE2T在前列腺癌发生中的首次功能特性。前列腺癌组织阵列分析证实了UBE2T在前列腺癌中的上调，尤其是那些发生远处转移的病例。此外，UBE2T表达水平较高与前列腺癌患者的预后较差相关。UBE2T的异位表达显著促进前列腺癌细胞的增殖、运动和侵袭，而通过shRNA敲低UBE2T则显著抑制前列腺癌细胞的这些能力。异种移植小鼠模型研究表明，UBE2T的过表达促进肿瘤形成和转移，而UBE2T的缺失则显著抑制肿瘤形成和转移。总体而言，我们确定了UBE2T在前列腺癌发生和发展中的关键作用。这些发现可能为未来旨在更全面地确定UBE2T作为潜在治疗靶点的研究提供框架。
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