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