MicroRNA-376b promotes breast cancer metastasis by targeting Hoxd10 directly

Exp Ther Med. 2017 Jan;13(1):79-84. doi: 10.3892/etm.2016.3942. Epub 2016 Dec 1.


Breast cancer is the most common malignant disease in women, and metastasis formed at distant anatomic sites was the major cause of cancer-related mortality. Thus, a novel therapy target and progression biomarker for breast cancer metastasis was necessary. microRNA (miR)-376b has been demonstrated to regulate angiogenesis; however, its role in cancer metastasis remains elusive. In the present study, the expression of miR-376b in normal breast tissue, JC and 4T1 cells was determined by qPCR. Furthermore, in vitro and in vivo experiments were performed to determine the effect of miR-376b on breast cancer metastasis. The direct target of miR-376b was determined by the luciferase assay and western blotting. The results indicated that silencing of miR-376b by the miR-376-mimic significantly inhibited 4T1 cell migration and invasion in vitro. Lung metastasis was also evidently decreased after silencing of miR-376b in 4T1 cells. Moreover, the luciferase assay and western blotting identified that Hoxd10 is the direct target of miR-376b during the regulation of breast cancer metastasis. To the best of our knowledge, the present study was the first to demonstrate the promoting breast cancer metastasis role of miR-376b by directly targeting Hoxd10. Therefore, it would be a novel therapy target and prognostic biomarker for breast cancer.

Keywords: Hoxd10; breast cancer; metastasis; microRNA-376b.