Cancer Management and Research (Feb 2020)
Demethylation of the Cosmc Promoter Alleviates the Progression of Breast Cancer Through Downregulation of the Tn and Sialyl-Tn Antigens
Abstract
Feng Xu,1,* Dong Wang,2,* JianXiu Cui,1 Jie Li,1 Hongchuan Jiang1 1Department of Breast Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, People’s Republic of China; 2Department of Oncology, Affiliated Hospital of Inner Mongolia University for Nationalities, Tongliao 028000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongchuan Jiang; Jie LiDepartment of Breast Surgery, Beijing Chao-Yang Hospital, Capital Medical University, No. 8, Gongti Nan Lu, Chaoyang District, Beijing 100020, People’s Republic of ChinaTel/Fax +86-1085231000Email [email protected]; [email protected]: 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.Keywords: breast cancer, cosmc, promoter methylation, Tn antigen, Sialyl-Tn antigen, prognosis
