miR-490-3p inhibits the growth and invasiveness in triple-negative breast cancer by repressing the expression of TNKS2.

ABSTRACT

Identification of key genes driving the aggressiveness of triple-negative breast cancer (TNBC) is important to develop effective therapies. In this study, we examined the expression and biological roles of microRNA (miR)-490-3p in TNBC. Our data showed that miR-490-3p-3p was underexpressed in TNBC compared with non-TNBC tissues (P=0.0021). Similarly, this miRNA was expressed at lower levels in TNBC cell lines than in non-TNBC cell lines. Gain-of-function studies revealed that miR-490-3p-3p overexpression inhibited cell growth and invasion in both MDA-MB-231 and MDA-MB-436 TNBC cells and impaired tumorigenesis of MDA-MB-231 cells in nude mice. Mechanistically, we found that miR-490-3p negatively regulated the expression of tankyrase 2 (TNKS2) via binding to its 3'-untranslated region and then blocked the activation of ß-catenin signaling. Importantly, overexpression of a miR-490-3p-resistant form of TNKS2 reversed miR-490-3p-mediated suppression of TNBC cell proliferation and invasion. Knockdown of TNKS2 via small interfering RNA technology was found to mimic the suppressive activity of miR-490-3p in MDA-MB-231 cells. Taken together, miR-490-3p is downregulated in TNBC and plays a suppressive role in cancer cell proliferation, invasion, and tumorigenesis. The tumor suppressive activity of miR-490-3p is largely mediated through downregulation of TNKS2 and inactivation of ß-catenin signaling. Thus, miR-490-3p may represent a potential therapeutic target for TNBC.