Department of Urology, The Fourth Affiliated Hospital of China Medical University, No. 4 Chongshan Road East, Huanggu District, Liaoning, Shenyang, China.
IUBMB Life. 2018 Apr;70(4):291-299. doi: 10.1002/iub.1717. Epub 2018 Mar 8.
The role of protein l-isoaspartate (d-aspartate) O-methyltransferase (PCMT1) in human cancer was generally cognized. The clinical significance and biological function of PCMT1 in bladder cancer is still unknown. PCMT1 mRNA and protein expression levels in bladder cancer tissues and cell lines were detected by qRT-PCR, immunohistochemistry, or western blot. The correlation between PCMT1 expression and clinicopathological factors was analyzed through immunohistochemistry in 108 bladder cancer patients. Loss-of-function and gain-of-function studies were conducted to explore the biological function of PCMT1 in bladder cancer cell lines in regulating cell proliferation, migration, and invasion. In our results, we found that PCMT1 was overexpressed in bladder cancer tissues compared with normal urothelium tissues in microarray datasets (GSE3167). Then, we confirmed PCMT1 mRNA and protein expression were increased in bladder cancer tissues and cell lines compared with paired normal urothelium tissues and normal uroepithelial cell line. PCMT1 protein expression was obviously correlated with clinical stage, muscularis invasion, lymph node metastasis, and distant metastasis. Survival analysis showed that PCMT1 protein high-expression was an independent unfavorable prognostic factor for bladder cancer patients. The in vitro experiments showed PCMT1 regulated bladder cancer cells migration and invasion through modulating epithelial-mesenchymal transition (EMT)-associated genes expression including E-cadherin, vimentin, Snail and Slug, but had no effect on proliferation. In conclusion, PCMT1 is an unfavorable prognostic biomarker and involves in cells migration and invasion through regulating EMT-associated genes. © 2018 IUBMB Life, 70(4):291-299, 2018.
蛋白质 l-异天冬氨酸（d-天冬氨酸）O-甲基转移酶（PCMT1）在人类癌症中的作用已被普遍认识。PCMT1 在膀胱癌中的临床意义和生物学功能尚不清楚。通过 qRT-PCR、免疫组织化学或 Western blot 检测膀胱癌组织和细胞系中 PCMT1 mRNA 和蛋白的表达水平。通过免疫组织化学分析 108 例膀胱癌患者中 PCMT1 表达与临床病理因素的相关性。通过失活和功能获得研究探讨 PCMT1 在膀胱癌细胞系中调节细胞增殖、迁移和侵袭的生物学功能。在我们的研究结果中，我们在微阵列数据集（GSE3167）中发现 PCMT1 在膀胱癌组织中的表达高于正常尿路上皮组织。然后，我们证实与配对的正常尿路上皮组织和正常尿路上皮细胞系相比，PCMT1 mRNA 和蛋白在膀胱癌组织和细胞系中表达增加。PCMT1 蛋白表达与临床分期、肌层浸润、淋巴结转移和远处转移明显相关。生存分析显示，PCMT1 蛋白高表达是膀胱癌患者独立的不良预后因素。体外实验表明，PCMT1 通过调节 EMT 相关基因的表达，包括 E-钙黏蛋白、波形蛋白、Snail 和 Slug，调节膀胱癌细胞的迁移和侵袭，但对增殖没有影响。总之，PCMT1 是一个不利的预后生物标志物，通过调节 EMT 相关基因参与细胞迁移和侵袭。
