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

doi:10.1016/j.isci.2023.106597

Combating breast cancer progression through combination therapy with hypomethylating agent and glucocorticoid

iScience. 2023 Apr 8;26(5):106597. doi: 10.1016/j.isci.2023.106597. eCollection 2023 May 19.

Authors

Affiliations

¹ Institute of Biotechnology, College of Life Science, National Tsing Hua University, Hsinchu, Taiwan.
² Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
³ Institute of Molecular Medicine, College of Life Science, National Tsing Hua University, Hsinchu, Taiwan.
⁴ Department of Medical Science, College of Life Science, National Tsing Hua University, Hsinchu, Taiwan.

Abstract

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.

Keywords: Cancer; Epigenetics; Molecular biology.