Abstract
Therapeutic applications of microRNA (miRNA) in KRAS-driven pancreatic cancers might be valuable, but few studies have explored this area. Here, we report that miR-96 directly targets the KRAS oncogene and functions as a tumor-suppressing miRNA in pancreatic cancer cells. Ectopic expression of miR-96 through a synthetic miRNA precursor inhibited KRAS, dampened Akt signaling, and triggered apoptosis in cells. In human clinical specimens, miR-96 was downregulated or deleted where an association with KRAS elevations was observed. In vitro and in vivo assays established that miR-96 decreased cancer cell invasion and migration and slowed tumor growth in a manner associated with KRAS downregulation. Our findings identify miR-96 as a potent regulator of KRAS, which may provide a novel therapeutic strategy for treatment of pancreatic cancer and other KRAS-driven cancers.
(c)2010 AACR.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3' Untranslated Regions
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Animals
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Apoptosis / physiology
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Cell Growth Processes / physiology
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Cell Line, Tumor
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Cell Movement / physiology
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Genes, Tumor Suppressor*
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Genes, ras
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Humans
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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MicroRNAs / biosynthesis
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MicroRNAs / genetics*
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Neoplasm Invasiveness
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Oncogene Protein v-akt / metabolism
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Pancreatic Neoplasms / genetics*
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Pancreatic Neoplasms / metabolism
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Pancreatic Neoplasms / pathology
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Proto-Oncogene Proteins / biosynthesis
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Proto-Oncogene Proteins / genetics*
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins p21(ras)
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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Signal Transduction
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Transfection
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ras Proteins / biosynthesis
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ras Proteins / genetics*
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ras Proteins / metabolism
Substances
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3' Untranslated Regions
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KRAS protein, human
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MIRN96 microRNA, human
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MicroRNAs
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Proto-Oncogene Proteins
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RNA, Messenger
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Oncogene Protein v-akt
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Proto-Oncogene Proteins p21(ras)
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ras Proteins