microRNA-200c downregulates XIAP expression to suppress proliferation and promote apoptosis of triple-negative breast cancer cells.

ABSTRACT

Despite advances in the understanding of breast cancer, patients most commonly have a poor prognosis, particularly those with triple negative breast cancer (TNBC). microRNAs (miRNAs) are endogenous non­coding small RNAs, and their aberrant expression is linked to numerous malignancies. In the present study, the expression levels of miR­200c in patients with TNBC were analyzed and it was identified that miR­200c was downregulated in TNBC samples, compared with that in normal adjacent tissues. miR­200c was overexpressed in the TNBC cell line MDA­MB­231 and its functions were studied in vitro and in vivo. An in vitro study revealed that the overexpression of miR­200c inhibited MDA­MB­231 cell proliferation and resulted in the induction of apoptosis. The in vivo data indicated that the overexpression of miR­200c significantly inhibited tumor growth and increased the rate of apoptosis. Target prediction revealed that the X­linked inhibitor of apoptosis (XIAP) had putative complementary sequences to miR­200c, which was confirmed by a dual luciferase reporter assay. Western blot analysis further demonstrated that the expression of XIAP was markedly reduced and that caspase­3 was highly activated by the overexpression of miR­200c. These findings suggested that miR­200c may function as a tumor suppressor gene in TNBC, at least partly via directly targeting XIAP, and may therefore act as a potential therapeutic target in the development of novel treatment strategies for TNBC.