Upregulation of miR-501-5p activates the wnt/β-catenin signaling pathway and enhances stem cell-like phenotype in gastric cancer

Background: mirnas are critical post-transcriptional regulators of gene expression and key mediators of tumourigenesis. mir-501-5p is newly identified to be involved in the tumor progression,but its biological role and mechanism remain largely unknown. this study is aimed to study the role of mir-501-5p in the progression of gastric cancer. methods: real-time pcr analysis was used to determine mir-501-5p expression in gastric cancer cell lines,clinical tissues and 112 clinicopathologically characterized gastric cancer specimens. the role of mir-501-5p in maintaining gastric cancer stem cell like phenotype was examined by tumor-sphere formation assay and expression of stem cell markers. luciferase reporter assay,cellular fractionation and western blot analysis were used to determined that mir-501-5p activated the wnt/β-catenin signaling by directly targeting dkk1,nkd1 and gsk3β. results: herein,our results revealed that mir-501-5p was markedly upregulated in gastric cancer cell lines and clinical tissues. high mir-501-5p levels predicted poor overall survival in gastric cancer patients. gain-of-function and loss-of-function studies showed that ectopic expression of mir-501-5p enhanced the cancer stem cell-like phenotype in gastric cancer cells. notably,wnt/β-catenin signaling was hyperactivated in gastric cancer cells that overexpress mir-501-5p,and mediated mir-501-5p-induced cancer stem cell-like phenotype. furthermore,mir-501-5p directly targeted and suppressed multiple repressors of the wnt/β-catenin signaling cascade,including dkk1,nkd1 and gsk3β. these results demonstrate that mir-501-5p maintains constitutively activated wnt/β-catenin signaling by directly targeting dkk1,nkd1 and gsk3β,which promotes gastric cancer stem cell like phenotype. conclusions: taken together,our findings reveal a new regulatory mechanism of mir-501-5p and suggest that mir-501-5p might be a potential target in gastric cancer therapy. © 2016 the author(s).