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The synergy between miR-486–5p and tamoxifen causes profound cell death of tamoxifen-resistant breast cancer cells.
- Source :
-
Biomedicine & Pharmacotherapy . Sep2021, Vol. 141, pN.PAG-N.PAG. 1p. - Publication Year :
- 2021
-
Abstract
- Breast cancer (BC) is the most common type of malignancy in women. A subset of breast cancers show resistance to endocrine-based therapies. The estrogen receptor (ER) plays a critical role in developing hormone-dependent BC. Loss of ER contributes to resistance to tamoxifen therapy and may contribute to mortality. Thus, it is crucial to overcome this problem. Here, using luciferase reporter assays, qRT-PCR, and Western blot analyses, we demonstrate that the microRNA miR-486–5p targets HMGA1 mRNA, decreasing its mRNA and protein levels in ER-positive (ER+) BC cells. Consistently, miR-486–5p is significantly downregulated, whereas HMGA1 is considerably upregulated in ER+ BC samples. Remarkably, while both miR-486–5p and tamoxifen individually cause G2/M cell cycle arrest, combination treatment synergistically causes profound cell death, specifically in tamoxifen-resistant ER+ cells but not in tamoxifen-sensitive ER+ cells. Combined treatment with miR-486–5p and tamoxifen also additively reduces cell migration, invasion, colony formation, mammary spheroid formation and a CD24-CD44+ cell population, representing decreased cancer stemness. However, these phenomena are independent of the tamoxifen responsiveness of the ER+ BC cells. Thus, miR-486–5p and tamoxifen exhibit additive and synergistic tumor-suppressive effects, most importantly causing profound cell death specifically in tamoxifen-resistant BC cells. Therefore, our work suggests that combining miR-486–5p replacement therapy with tamoxifen treatment is a promising strategy to treat endocrine therapy-resistant BC. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 07533322
- Volume :
- 141
- Database :
- Academic Search Index
- Journal :
- Biomedicine & Pharmacotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 152232426
- Full Text :
- https://doi.org/10.1016/j.biopha.2021.111925