Combating breast cancer progression through combination therapy with hypomethylating agent and glucocorticoid
Journal
iScience
Journal Volume
26
Journal Issue
5
Date Issued
2023-05-19
Author(s)
Chu, Yu-Hsin
Huang, Yi-Chen
Chiu, Pei-Yun
Pan, Yan-Ru
Kuo, Yuan-Ting
Wang, Rong-Hsuan
Kao, Yu-Chin
Wang, Yi-Hsiang
Lin, Yi-Fan
Lin, Kai-Ti
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.
Subjects
Cancer
Epigenetics
Molecular biology
SDGs
Type
journal article