Mir-629 promotes human pancreatic cancer progression by targeting foxo3

Abstract

The FOXO signaling pathway has been reported to have an important role in human cancer. Expression of miR-629 was markedly upregulated in pancreatic cancer and negatively correlated with FOXO3. Therefore, exploring the regulatory mechanism of miR-629 and FOXO3 signaling may provide valuable clinical targets for pancreatic cancer therapy. In the current study, we found that overexpressing and inhibiting miR-629, respectively, enhanced and reduced the cell proliferation and metastasis of pancreatic cancer cells in vitro and in vivo compared with parental cells or cells transfected with a control vector. Furthermore, we found that miR-629 negatively regulated FOXO3 protein expression and decreased the activity of a luciferase reporter construct containing the FOXO3 3′-untranslated region. These results show that miR-629 regulates FOXO3 at the posttranscriptional level, resulting in enhanced cell proliferation and invasion of pancreatic carcinoma. Furthermore, we found that overexpressing miR-629 enhanced, while inhibiting miR-629 reduced, the stem cell-like phenotype of pancreatic cancer cells in vitro. A functional polymorphism at miR-629-binding site in the 3′-UTR of FOXO3 gene confers a decreased risk of progression in pancreatic carcinoma. Furthermore, these findings suggest that miR-629 has a vital role in promoting the development of pancreatic cancer and may represent a novel prognostic biomarker and therapeutic target.