miR-365 inhibits cell invasion and migration of triple negative breast cancer through ADAM10.
Fei Liu, Liang Zhuang, Ruxing Wu, Dingyu Li
Abstract
PURPOSE: Triple negative breast cancer (TNBC) refers to breast cancer that lacks progesterone receptor (PR), estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2). MicroRNA-365 (miR-365), a new-found microRNA, has been reported to possess significant functions in a multitude of human cancers. The purpose of this study was to detect thoroughly the molecular mechanisms of miR-365 that underlie the progress of TNBC. METHODS: The mRNA levels of miR-365 and A Disintegrin and Metalloprotease 10 (ADAM10) were measured by real-time polymerase chain reaction (RT-PCR). Luciferase activity report was applied to verify that ADAM10 was a direct target gene of miR-365. Cell proliferation ability was measured by MTT assay. Transwell assay was utilized to test cell migratory and invasive abilities. RESULT: We found that miR-365 was low-expressed in breast cancer tissues and 5 TNBC cell lines compared with the paracancerous samples and a normal cell line MCF10A. Meanwhile, we discovered that the expression of ADAM10 was higher in the 5 TNBC cell lines than in the normal cell line MCF10A. The proliferation, migration and invasion abilities were suppressed by overexpression of miR-365, whereas they were enhanced by interfering miR-365 in breast cancer. The luciferase reporter assay demonstrated that miR-365 directly targeted ADAM10 through directly binding to the 3'-untranslated region (3'-UTR). And the expression of ADAM10 was reduced by exogenous overexpression of miR-365, while it was increased by transfecting of miR-365 inhibitor in MDA-MB-231 and BT483 cells. Furthermore, re-expression of ADAM10 reversed partial functions of the suppressive roles on cell proliferation, migration and invasion by miR-365 TNBC. CONCLUSIONS: MiR-365 inhibited the proliferation, migration and invasion through directly binding to the 3'-UTR of ADAM10 mRNA in TNBC. It is suggested that miR-365/ADAM10 axis may present a new target for the treatment of breast cancer.