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Cosmc启动子的去甲基化通过下调Tn和唾液酸化Tn抗原减轻乳腺癌进展。

Demethylation of the Cosmc Promoter Alleviates the Progression of Breast Cancer Through Downregulation of the Tn and Sialyl-Tn Antigens.

作者信息

Xu Feng, Wang Dong, Cui JianXiu, Li Jie, Jiang Hongchuan

机构信息

Department of Breast Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, People's Republic of China.

Department of Oncology, Affiliated Hospital of Inner Mongolia University for Nationalities, Tongliao 028000, People's Republic of China.

出版信息

Cancer Manag Res. 2020 Feb 11;12:1017-1027. doi: 10.2147/CMAR.S214553. eCollection 2020.

DOI:10.2147/CMAR.S214553
PMID:32104083
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7023867/
Abstract

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.

摘要

背景

乳腺癌中的异常基因甲基化与不良预后相关。此外，异常的Cosmc可诱导Tn和STn抗原的表达。本研究旨在通过调控Tn和STn抗原，探讨Cosmc启动子甲基化在乳腺癌中的作用。

方法

测定乳腺癌细胞系中Cosmc以及Tn和STn抗原的表达模式。通过体外和体内实验，过表达Cosmc以探究其对细胞行为的影响，包括乳腺癌细胞的生长、迁移、侵袭和凋亡以及肿瘤生长。随后，使用甲基转移酶和甲基转移酶抑制剂改变Cosmc的甲基化状态，以探究与Cosmc启动子甲基化相关的机制。

结果

Cosmc在乳腺癌细胞中表达较低。Cosmc过表达在体外抑制乳腺癌细胞的生长、迁移和侵袭，同时促进其凋亡，在体内抑制肿瘤生长。发现Cosmc启动子甲基化降低了乳腺癌中Cosmc的水平，并增加了Tn和STn抗原的表达。

结论

总之，Cosmc的去甲基化通过抑制Tn和STn抗原减轻乳腺癌进展，这为针对乳腺癌的新靶点治疗提供了依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c34b/7023867/1ae0bcf39d97/CMAR-12-1017-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c34b/7023867/ec29dffda900/CMAR-12-1017-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c34b/7023867/39d88a069f7c/CMAR-12-1017-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c34b/7023867/beb76831f276/CMAR-12-1017-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c34b/7023867/1a68a697a745/CMAR-12-1017-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c34b/7023867/1ae0bcf39d97/CMAR-12-1017-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c34b/7023867/ec29dffda900/CMAR-12-1017-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c34b/7023867/39d88a069f7c/CMAR-12-1017-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c34b/7023867/beb76831f276/CMAR-12-1017-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c34b/7023867/1a68a697a745/CMAR-12-1017-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c34b/7023867/1ae0bcf39d97/CMAR-12-1017-g0005.jpg

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