Abstract
In the present study, we demonstrated that the levels of DKK1 were decreased in serums and tissues of GC. DKK1 levels inversely correlated with tumor class, TNM stage, distant metastasis and lymph node metastasis of GC. GC patients with low DKK1 levels had a poor overall survival. DKK1 inhibited the proliferation of GC cells in vitro and in vivo. DKK1 also inhibited invasion, but enhanced chemo-sensitivity of GC cells. Mechanically, miR-493 levels increased in GC and directly targeted and down-regulated DKK1 expression. In agreement, miR-493 promoted proliferation of GC cells in vitro and in vivo. MiR-493 also promoted invasion and chemo-resistance of GC cells. However, DKK1 overexpression reversed the effects of miR-493 on proliferation, invasion and chemo-sensitivity. Thus, our results provide new insight for the role of miR-493/DKK1 axis in GC.
Keywords:
DKK1; gastric cancer; invasion; miR-493; proliferation.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents / pharmacology
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Apoptosis
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Blotting, Western
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Case-Control Studies
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Cell Movement
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Cell Proliferation
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Cohort Studies
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Down-Regulation
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Drug Resistance, Neoplasm / genetics*
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Follow-Up Studies
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Gene Expression Regulation, Neoplastic*
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Humans
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Immunoenzyme Techniques
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Intercellular Signaling Peptides and Proteins / genetics
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Intercellular Signaling Peptides and Proteins / metabolism*
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Lymphatic Metastasis
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Mice
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MicroRNAs / genetics*
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Neoplasm Grading
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Neoplasm Invasiveness
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Neoplasm Staging
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Prognosis
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RNA, Messenger / genetics
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Real-Time Polymerase Chain Reaction
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Reverse Transcriptase Polymerase Chain Reaction
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Stomach Neoplasms / drug therapy*
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Stomach Neoplasms / genetics
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Stomach Neoplasms / pathology*
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Survival Rate
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Tumor Cells, Cultured
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Xenograft Model Antitumor Assays
Substances
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Antineoplastic Agents
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DKK1 protein, human
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Intercellular Signaling Peptides and Proteins
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MIRN493 microRNA, human
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MicroRNAs
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RNA, Messenger