• Dr. Roger Moorehead
• Katrina Watson

Claudin-low breast cancer cells, a subset of triple-negative breast cancer, exhibit mesenchymal characteristics and express remarkably low levels of the miR-200 micro-RNA family. Therefore, this research examines the cellular and functional impact of restoring miR-200 expression in a human claudin-low breast cancer cell line MDA-MB-231. MDA-MB-231 cells were stably transfected with the miR-200c/141 cluster (MDA-231c141) or a control vector (MDA-231EV). The overexpression of the miR-200c/141 cluster in the MDA-231c141 cells reverted cell morphology to a more epithelial phenotype and significantly reduced cell proliferation and migration in vitro. Additionally, injection of MDA-231c141 cells into the 4th mammary gland of NCG mice resulted in significantly impaired tumor growth than MDA-231EV produced tumors. Furthermore, RNA sequencing identified MXRA8 as being downregulated in MDA-231c141 tumors. Subsequently, qRT-PCR and Western blotting confirmed that MXRA8 expression was significantly higher in mammary tumors induced by MDA-231EV cells compared to those induced by MDA-231c141 cells and immunohistochemistry revealed that the levels of MXRA8 remained high in metastatic tumor cells found in the lungs. Therefore, our data suggests that miR-200s reduce proliferation and migration of claudin-low mammary tumor cells in vitro and inhibit growth and metastasis in vivo through downregulating MXRA8 expression.