Demethylation of the Cosmc Promoter Alleviates the Progression of Breast Cancer Through Downregulation of the Tn and Sialyl-Tn Antigens (Retracted article. See vol. 14, pg. 3119, 2022)
Demethylation of the Cosmc Promoter Alleviates the Progression of Breast Cancer Through Downregulation of the Tn and Sialyl-Tn Antigens (Retracted article. See vol. 14, pg. 3119, 2022)
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Cosmc 启动子的去甲基化通过下调 Tn 和唾液酸 Tn 抗原来减缓乳腺癌的进展
DOI：
10.2147/cmar.s214553
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发表时间：
2020-01-01
影响因子：
3.3
通讯作者：
Jiang, Hongchuan
中科院分区：
文献类型：
--
作者：
Xu, Feng;Wang, Dong;Jiang, Hongchuan
背景：乳腺癌中基因甲基化异常与预后不良有关。此外，COSMC异常还可诱导TN和STN抗原表达。本研究旨在通过对TN和STN抗原的调控，探讨Cosmc基因启动子甲基化在乳腺癌中的作用。通过体外和体内实验，探讨Cosmc过表达对乳腺癌细胞生长、迁移、侵袭、凋亡和肿瘤生长的影响。然后用甲基转移酶和甲基转移酶抑制剂改变Cosmc的甲基化状态，以探讨Cosmc启动子甲基化的相关机制。COSMc过表达在体外抑制乳腺癌细胞的生长、迁移和侵袭，同时促进细胞的凋亡，抑制体内肿瘤的生长。Cosmc启动子甲基化可降低乳腺癌中Cosmc的表达水平，增加TN和STN抗原的表达。结论：Cosmc基因去甲基化通过抑制TN和STN抗原抑制乳腺癌的进展，为寻找新的乳腺癌治疗靶点提供了依据。
Background: Aberrant gene methylation in breast cancer is associated with an unfavorable prognosis. Besides, abnormal Cosmc can induce the expression of Tn and STn antigens. The present study aimed to investigate the roles of Cosmc promoter methylation in breast cancer through the regulation of Tn and STn antigens.Methods: The expression patterns of Cosmc and the Tn and STn antigens in breast cancer cell lines were determined. Cosmc was overexpressed to explore the effects of Cosmc on cell behavior, including the growth, migration, invasion, and apoptosis of breast cancer cells and tumor growth with in vitro and in vivo experiments. Afterwards, a methyltransferase and a methyltransferase inhibitor were used to alter the methylation status of Cosmc to explore the mechanisms related to Cosmc promoter methylation.Results: Cosmc was poorly expressed in breast cancer cells. Cosmc overexpression inhibited cell growth, migration, and invasion while promoting apoptosis in breast cancer cells in vitro and restraining tumor growth in vivo. Cosmc promoter methylation was found to decrease the levels of Cosmc and increased the expression of the Tn and STn antigens in breast cancer.Conclusion: In conclusion, the demethylation of Cosmc mitigates breast cancer progression through the repression of the Tn and STn antigens, which provides evidence for therapeutic considerations for a novel target against breast cancer.