Abstract
We discovered the expression level of miR-148a significantly decreased in pancreatic cancer tissues whereas that of DNMT1 increased. In ASPC-1 cancer cells, the overexpression of miR-148a led to a decreased level of DNMT1 and reduced the proliferation and metastasis of ASPC-1 cells. Moreover, the increased expression of miR-148a arrested the UTR methylation of p27, giving rise to an increased level of p27. Interestingly, it was shown that the DNMT1 inhibition enhanced the expression of miR-148a. In vivo studies demonstrated that the tumorigenesis of ASPC-1 was significantly arrested by either the overexpression of miR-148a or the inhibition of DNMT1.
Keywords:
DNMT1; Pancreatic cancer; Senescence; miR-148a; p27.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Line, Tumor
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Cyclin-Dependent Kinase Inhibitor p27 / genetics*
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DNA (Cytosine-5-)-Methyltransferase 1
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DNA (Cytosine-5-)-Methyltransferases / genetics*
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DNA Methylation
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Gene Expression Regulation, Neoplastic
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Humans
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Mice
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MicroRNAs / genetics*
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Molecular Targeted Therapy
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Neoplasm Metastasis
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Neoplasm Transplantation
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Pancreatic Neoplasms / genetics*
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Pancreatic Neoplasms / therapy*
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Untranslated Regions
Substances
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CDKN1B protein, human
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MIRN148 microRNA, human
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MicroRNAs
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Untranslated Regions
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Cyclin-Dependent Kinase Inhibitor p27
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DNA (Cytosine-5-)-Methyltransferase 1
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DNA (Cytosine-5-)-Methyltransferases
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DNMT1 protein, human
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Dnmt1 protein, mouse