miR-181c promotes proliferation via suppressing PTEN expression in inflammatory breast cancer

Abstract

Primary inflammatory breast cancer (IBC) accounts for ∼6% of new breast cancer cases. Even with multimodality treatment, the 5-year disease-free survival is <45%, thus making IBC the most deadly form of locally advanced breast cancer. Better understanding of the pathogenesis of IBC is essential to the design of effective therapy. We found that miR-181c was upregulated in IBC, implying that it could be a useful prognostic marker for IBC and a novel therapeutic target for the intervention of disease. Elucidating why the gene is overexpressed and how to downregulate it will help us to further understand the pathogenesis and progression of the disease and offer new targets for therapies. In this study, we showed that miR-181c as an oncogene promoted proliferation and it inhibited PTEN protein expression by targeting 3′-UTR of PTEN mRNA in IBC SUM149 cells. Moreover, PTEN was not only downregulated in IBC, but also inhibited proliferation in SUM149 cells and introduction of PTEN cDNA lacking the predicted sites of 3′-UTR abrogated miR-181c cellular function, suggesting that miR-181c inhibited proliferation by downregulating PTEN expression in IBC. Thus, targeting miR-181c and restoration of PTEN can be used in conjunction with other therapies to prevent progression of IBC.