MicroRNA-206 inhibits metastasis of triple-negative breast cancer by targeting transmembrane 4 L6 family member 1.

ABSTRACT

Purpose: Breast cancer (BC) is a common malignancy in women, but the survival rate for BC is not very encouraging. Especially for triple-negative breast cancer (TNBC), a kind of breast cancer that does not have any of the receptors that are commonly found in BC. We investigated the impact of microRNA-206 (miR-206) on transmembrane 4 L6 family member 1 (TM4SF1) in TNBC for therapeutic purpose. Patients and methods: Twenty BC tissues from diagnosed BC patients were analyzed via real-time PCR and Western blotting for expression of TM4SF1 and miR-206. The expression of TM4SF1 was studied in relationship with miR-206 in MDA-MB-231 cells. The biological impact of TM4SF1 and miR-206 on MDA-MB-231 cells and BALB/c nude mice model was studied using proliferation, transwell migration, and invasion assays both in vitro and in vivo. Results: The expression of TM4SF1 in BC tissues was significantly higher than that in adjacent normal breast tissues. In contrast, miR-206 showed a decreased expression level in BC tissues, especially for subtype basal like. Overexpression of miR-206 in MDA-MB-231 cells by transfecting miR-206 resulted in downregulation of TM4SF1. In contrast, knockdown miR-206 expression reversed miR-206-mediated phenotype in MDA-MB-231 cells. Expression level of TM4SF1 in MDA-MB-231 cells was associated with cell migration and invasion capabilities in vitro. Breast tumor burden was correlated with the expression level of TM4SF1 in vivo. Conclusion: Taken together, our results showed the involvement of TM4SF1 in TNBC migration and invasion. miR-206 negatively regulated gene expression of TM4SF1. These findings indicate that miR-206 could be used as a potential therapeutic agent for TNBC.