دورية أكاديمية
The synergy between miR-486–5p and tamoxifen causes profound cell death of tamoxifen-resistant breast cancer cells
| العنوان: | The synergy between miR-486–5p and tamoxifen causes profound cell death of tamoxifen-resistant breast cancer cells |
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| المؤلفون: | Mansoori, Behzad, Najafi, Souzan, Mohammadi, Ali, AsadollahSeraj, Haleh, Savadi, Pouria, Mansoori, Behnaz, Nazari, Afsaneh, Mokhtarzadeh, Ahad, Roshani, Elmira, Duijf, Pascal HG, Cho, William Chi Shing, Baradaran, Behzad |
| المصدر: | Mansoori , B , Najafi , S , Mohammadi , A , AsadollahSeraj , H , Savadi , P , Mansoori , B , Nazari , A , Mokhtarzadeh , A , Roshani , E , Duijf , P HG , Cho , W C S & Baradaran , B 2021 , ' The synergy between miR-486–5p and tamoxifen causes profound cell death of tamoxifen-resistant breast cancer cells ' , Biomedicine and Pharmacotherapy , vol. 141 , 111925 . https://doi.org/10.1016/j.biopha.2021.111925Test |
| سنة النشر: | 2021 |
| المجموعة: | University of Southern Denmark: Research Output / Syddansk Universitet |
| مصطلحات موضوعية: | Breast cancer, Drug-resistant, HMGA1, MiR-486–5p, Tamoxifen |
| الوصف: | 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. ; 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 ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://portal.findresearcher.sdu.dk/da/publications/73f8e760-8f5e-402a-9cbe-3bcefe8b8614Test |
| DOI: | 10.1016/j.biopha.2021.111925 |
| الإتاحة: | https://doi.org/10.1016/j.biopha.2021.111925Test https://portal.findresearcher.sdu.dk/da/publications/73f8e760-8f5e-402a-9cbe-3bcefe8b8614Test https://findresearcher.sdu.dk/ws/files/185097093/Open_Access_Version.pdfTest |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.6A8554DE |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.biopha.2021.111925 |
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