Upregulation of miR-543-3p promotes growth and stem cell-like phenotype in bladder cancer by activating the Wnt/β-catenin signaling pathway.

The Wnt/β-catenin signaling pathway, which is strictly controlled by multiple negative regulators, has been reported commonly hyper activated and closely related to the progression of bladder cancer. However, how tumor cells override the negative regulatory effects to maintain constitutive activation of Wnt/β-catenin signaling is still unclear. In the current study, we demonstrated that upregulation of miR-543-3p in bladder cancer activated Wnt/β-catenin signaling by directly targeting Wnt inhibitory factor 1 (WIF1) and Dickkopf 1 (DKK1), which are important antagonist molecules of the Wnt/β-catenin pathway. Expression of miR-543-3p was upregulated in both bladder cancer tissues and cells, and positively correlated with high-grade bladder cancer. Furthermore, ectopic overexpression of miR-543-3p promoted proliferation and inhibited apoptosis in bladder cancer cells. Notably, overexpression of miR-543-3p enhanced, while silencing miR-543-3p reduced, stem cell-like phenotype of bladder cancer cells. Therefore, our results suggest that miR-543-3p plays a significant role in promoting proliferation and stem cell-like phenotype in bladder cancer, which might be a potential target for anti-bladder cancer therapy. IJCEP