Combating breast cancer progression through combination therapy with hypomethylating agent and glucocorticoid
Yu-Hsin Chu,
Yi-Chen Huang,
Pei-Yun Chiu,
Wen-Hung Kuo,
Yan-Ru Pan,
Yuan-Ting Kuo,
Rong-Hsuan Wang,
Yu-Chin Kao,
Yi-Hsiang Wang,
Yi-Fan Lin,
Kai-Ti Lin
Affiliations
Yu-Hsin Chu
Institute of Biotechnology, College of Life Science, National Tsing Hua University, Hsinchu, Taiwan
Yi-Chen Huang
Institute of Biotechnology, College of Life Science, National Tsing Hua University, Hsinchu, Taiwan
Pei-Yun Chiu
Institute of Biotechnology, College of Life Science, National Tsing Hua University, Hsinchu, Taiwan
Wen-Hung Kuo
Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
Yan-Ru Pan
Institute of Biotechnology, College of Life Science, National Tsing Hua University, Hsinchu, Taiwan
Yuan-Ting Kuo
Institute of Biotechnology, College of Life Science, National Tsing Hua University, Hsinchu, Taiwan
Rong-Hsuan Wang
Institute of Biotechnology, College of Life Science, National Tsing Hua University, Hsinchu, Taiwan
Yu-Chin Kao
Institute of Biotechnology, College of Life Science, National Tsing Hua University, Hsinchu, Taiwan
Yi-Hsiang Wang
Institute of Molecular Medicine, College of Life Science, National Tsing Hua University, Hsinchu, Taiwan
Yi-Fan Lin
Institute of Biotechnology, College of Life Science, National Tsing Hua University, Hsinchu, Taiwan
Kai-Ti Lin
Institute of Biotechnology, College of Life Science, National Tsing Hua University, Hsinchu, Taiwan; Department of Medical Science, College of Life Science, National Tsing Hua University, Hsinchu, Taiwan; Corresponding author
Summary: Breast cancer is the leading cause of cancer-related death in women. Among breast cancer types, triple-negative breast cancer (TNBC) accounts for 15% of all breast cancers with aggressive tumor behavior. By using bioinformatic approaches, we observed that the microRNA-708 promoter is highly methylated in breast carcinomas, and this methylation is linked to a poor prognosis. Moreover, microRNA-708 expression correlates with better clinical outcomes in TNBC patients. Combination treatment with the hypomethylating agent decitabine and synthetic glucocorticoid significantly increased the expression of microRNA-708, reactivated DNMT-suppressed pathways, and decreased the expression of multiple metastasis-promoting genes such as matrix metalloproteinases (MMPs) and IL-1β, leading to the suppression of breast cancer cell proliferation, migration, and invasion, as well as reduced tumor growth and distant metastasis in the TNBC xenograft mouse model. Overall, our study reveals a therapeutic opportunity in which a combined regimen of decitabine with glucocorticoid may have therapeutic potential in treating TNBC patients.
