چاپ صفحه |  صفحه نخست سامانه |  چکیده مقاله |  نویسندگان |  دانلود مقاله | دانشگاه علوم پزشکی تبریز |
| 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. |
| نویسنده | نفر چندم مقاله |
|---|---|
| بهزاد منصوری | اول |
| سوزان نجفی | دوم |
| امیر علی مختارزاده | هشتم |
| بهزاد برادران | دوازدهم |
| پوریا سوادی صومعه | پنجم |
| نام فایل | تاریخ درج فایل | اندازه فایل | دانلود |
|---|---|---|---|
| 543-The synergy between miR-486-5p and tamoxifen causes profound cell death of tamoxifen-resistant cancer cells.pdf | 1400/05/12 | 7469185 | دانلود |
