MiR-1207 overexpression promotes cancer stem cell-like traits in ovarian cancer by activating the Wnt/β-catenin signaling pathway

Oncotarget. 2015 Oct 6;6(30):28882-94. doi: 10.18632/oncotarget.4921.

Abstract

Wnt/β-catenin signaling pathway is strictly controlled by multiple negative regulators. However, how tumor cells override the negative regulatory effects to maintain constitutive activation of Wnt/β-catenin signaling, which is commonly observed in various cancers, remains puzzling. In current study, we reported that overexpression of miR-1207 in ovarian cancer activated Wnt/β-catenin signaling by directly targeting and suppressing secreted Frizzled-related protein 1 (SFRP1), AXIN2 and inhibitor of β-catenin and TCF-4 (ICAT), which are vital negative regulators of the Wnt/β-catenin pathway. We found that the expression of miR-1207 was ubiquitously upregulated in both ovarian cancer tissues and cells, which inversely correlated with patient overall survival. Furthermore, overexpression of miR-1207 enhanced, while silencing miR-1207 reduced, stem cell-like traits of ovarian cancer cells in vitro and in vivo, including tumor sphere formation capability and proportion of SP+ and CD133+ cells. Importantly, upregulating miR-1207 promoted, while silencing miR-1207 inhibited, the tumorigenicity of ovarian cancer cells. Hence, our results suggest that miR-1207 plays a vital role in promoting the cancer stem cell-like phenotype in ovarian cancer and might represent a potential target for anti-ovarian cancer therapy.

Keywords: Wnt/β-catenin signaling; cancer stem cells; ovarian cancer; tumorigenicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • Adaptor Proteins, Signal Transducing
  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Axin Protein / genetics
  • Axin Protein / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glycoproteins / genetics
  • Glycoproteins / metabolism
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • Oligonucleotides, Antisense / genetics
  • Oligonucleotides, Antisense / metabolism
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Ovarian Neoplasms / therapy
  • Peptides / genetics
  • Peptides / metabolism
  • Phenotype
  • Time Factors
  • Transfection
  • Tumor Burden
  • Up-Regulation
  • Wnt Signaling Pathway* / genetics
  • beta Catenin / genetics
  • beta Catenin / metabolism*

Substances

  • AC133 Antigen
  • AXIN2 protein, human
  • Adaptor Proteins, Signal Transducing
  • Antigens, CD
  • Axin Protein
  • CTNNB1 protein, human
  • CTNNBIP1 protein, human
  • Glycoproteins
  • Intercellular Signaling Peptides and Proteins
  • Intracellular Signaling Peptides and Proteins
  • MIRN1207 microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • Oligonucleotides, Antisense
  • PROM1 protein, human
  • Peptides
  • Prom1 protein, mouse
  • SFRP1 protein, human
  • beta Catenin