Abstract
MicroRNAs (miRNAs) are small noncoding RNAs that are involved in various diseases, including cancer. In the present study, we found that miR-216b was downregulated in nasopharyngeal carcinoma (NPC) cell lines and specimens. Decreased expression of miR-216b was directly related to advanced clinical stage and lymph node metastasis. miR-216b levels correlated inversely with levels of KRAS protein during nasopharyngeal tumorigenesis. Furthermore, we demonstrated that miR-216b can bind to the 3' untranslated region (UTR) of KRAS and inhibit expression of the KRAS protein. Both in vitro and in vivo assays revealed that miR-216b attenuated NPC cell proliferation, invasion and tumor growth in nude mice. miR-216b exerts its tumor suppressor function through inhibition of the KRAS-related AKT and ERK pathways. Our findings provide, for the first time, significant clues regarding the role of miR-216b as a tumor suppressor by targeting KRAS in NPC.
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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Carcinoma
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Cell Growth Processes / genetics
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Cell Line, Tumor
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Down-Regulation
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Gene Expression Regulation, Neoplastic
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Gene Knockdown Techniques
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Genes, ras*
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Humans
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Immunohistochemistry
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MAP Kinase Signaling System
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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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MicroRNAs / metabolism
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Nasopharyngeal Carcinoma
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Nasopharyngeal Neoplasms / genetics*
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Nasopharyngeal Neoplasms / metabolism
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Nasopharyngeal Neoplasms / pathology*
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Proto-Oncogene Proteins / antagonists & inhibitors
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Proto-Oncogene Proteins / biosynthesis
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins c-akt / antagonists & inhibitors
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Proto-Oncogene Proteins c-akt / genetics
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Proto-Oncogene Proteins c-akt / metabolism
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Proto-Oncogene Proteins p21(ras)
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Transfection
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ras Proteins / antagonists & inhibitors
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ras Proteins / biosynthesis
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ras Proteins / genetics
Substances
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3' Untranslated Regions
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KRAS protein, human
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MicroRNAs
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-akt
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Extracellular Signal-Regulated MAP Kinases
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Proto-Oncogene Proteins p21(ras)
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ras Proteins