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O-糖基化乙酰化促进膀胱癌细胞的恶性表型。

O-GlcNAcylation promotes malignant phenotypes of bladder cancer cells.

机构信息

Department of Urology, The Second Affiliated Hospital of Soochow University, Soochow University, Suzhou, China.

Department of Medical Records, The Second Affiliated Hospital of Soochow University, Soochow University, Suzhou, China.

出版信息

Neoplasma. 2020 Jul;67(4):880-888. doi: 10.4149/neo_2020_191006N1009. Epub 2020 Apr 16.

Abstract

O-GlcNAcylation (O-GlcNAc) is a posttranslational modification that is mediated by O-GlcNAc-transferase (OGT) and reversed by O-GlcNAcase (OGA). Increasing evidence indicates that protein O-GlcNAcylation is increased in various types of cancer. In the present study, we aimed to evaluate the expression and function of both OGT and OGA in bladder cancer cells in vitro and in vivo. Expression data of OGT and OGA at the mRNA level was obtained from the Oncomine database. Effects of OGT and OGA on cell proliferate, invasive, and migratory abilities were assessed using MTT, wound healing, cell invasive assay, and cell cycle analysis. In vivo assay was also performed in nude mice. The results revealed that the expression of OGT in bladder cancer tissues was higher than that of normal tissues, while the OGA level was found to be lower in cancer tissues. We also found that knockdown of OGT could inhibit cell proliferation, migration, invasion, and induce cell cycle arrest, while these are reversed when OGA is inhibited. We also observed that O-GlcNAcylation could promote tumor formation in vivo, compared with a negative control. In summary, this study describes the oncogenic role of O-GlcNAcylation in bladder cancer cells.

摘要

O-连接的 N-乙酰氨基葡萄糖基化(O-GlcNAc)是一种由 O-连接的 N-乙酰氨基葡萄糖基转移酶(OGT)介导并由 O-连接的 N-乙酰氨基葡萄糖苷酶(OGA)逆转的翻译后修饰。越来越多的证据表明,蛋白质 O-GlcNAc 化在各种类型的癌症中增加。在本研究中,我们旨在评估 OGT 和 OGA 在膀胱癌细胞中的表达和功能。从 Oncomine 数据库获得 OGT 和 OGA 的 mRNA 水平的表达数据。使用 MTT、划痕愈合、细胞侵袭测定和细胞周期分析评估 OGT 和 OGA 对细胞增殖、侵袭和迁移能力的影响。还在裸鼠中进行了体内试验。结果表明,膀胱癌组织中 OGT 的表达高于正常组织,而 OGA 水平在癌症组织中较低。我们还发现,敲低 OGT 可抑制细胞增殖、迁移、侵袭并诱导细胞周期停滞,而抑制 OGA 时则会逆转这些作用。我们还观察到,与阴性对照相比,O-GlcNAc 化可促进体内肿瘤形成。总之,本研究描述了 O-GlcNAc 化在膀胱癌细胞中的致癌作用。

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