MiR-939 promotes the proliferation of human ovarian cancer cells by repressing APC2 expression

Biomed Pharmacother. 2015 Apr:71:64-9. doi: 10.1016/j.biopha.2015.02.020. Epub 2015 Feb 26.

Abstract

Aberrant activation of the Wnt/β-catenin signal pathway is frequently observed in various human cancers. Therefore, it was speculated that adenomatous polyposis coli 2 (APC2) could play important roles in activating the Wnt/β-catenin pathway. In this present study, miR-939 expression was markedly upregulated in ovarian cancer tissues and ovarian cancer cells. In functional assays, Overexpression of miR-939 promoted the proliferation and anchorage-independent growth of ovarian cancer cells, whereas inhibition of miR-939 inhibited this effect. Bioinformatics analysis further revealed APC2, a putative tumor suppressor as a potential target of miR-939. Result of luciferase reporter assays showed that miR-939 directly binds to the 3'-untranslated region (3'-UTR) of APC2 mRNA. Furthermore, we demonstrated that miR-939 could reduce the Wnt/β-catenin signal pathway by suppressing APC2 directly, resulting in increasing expression of CyclinD1, MYC and TCF. In functional assays, APC2-silenced in miR-939-in-transfected ES-2 cells have positive effect to promote cell proliferation, suggesting that direct APC2 downregulation is required for miR-939-induced ovarian cancer cell proliferation. In sum, our data provided compelling evidence that miR-939 functioned as a potential tumor promoter by regulating the Wnt/β-catenin signal pathway through direct suppression of APC2 expression and might sever as a potential therapeutic target for ovarian cancer patients.

Keywords: APC2; Cell proliferation; Human ovarian cancer; miR-939.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Base Sequence
  • Cell Line, Tumor
  • Cell Proliferation
  • Cytoskeletal Proteins / genetics*
  • Cytoskeletal Proteins / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Molecular Sequence Data
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology*
  • Protein Binding / genetics
  • Up-Regulation / genetics

Substances

  • 3' Untranslated Regions
  • APC2 protein, human
  • Cytoskeletal Proteins
  • MIRN939 microRNA, human
  • MicroRNAs