Abstract
microRNAs (miRNAs) have been suggested to play a vital role in regulating tumor progression and invasion. However, the expression of miR-27a in esophageal squamous cell carcinoma (ESCC) and its effect on the tumorigenesis of ESCC are unclear. In the present study, we found that miR-27a was downregulated in esophageal carcinoma cell lines and ESCC specimens with lymph node metastasis. Furthermore, we demonstrated that miR-27a binds to the 3'-untranslated region (UTR) of KRAS and inhibits the expression of the KRAS protein. miR-27a levels were inversely correlated with levels of KRAS mRNA and protein in ESCC specimens. Both in vitro and in vivo assays revealed that miR-27a attenuated ESCC proliferation, invasion and tumor growth in nude mice. miR-27a exerts its tumor suppressor function through inhibition of the KRAS-related ERK pathways. Our findings suggest, for the first time, that miR-27a suppresses tumorigenesis of ESCC by targeting KRAS.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3' Untranslated Regions / genetics
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Animals
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Carcinoma, Squamous Cell / genetics*
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Carcinoma, Squamous Cell / pathology
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Cell Line, Tumor
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Cell Movement / genetics
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Cell Proliferation
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Cell Transformation, Neoplastic / genetics*
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Cell Transformation, Neoplastic / pathology
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Down-Regulation
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Esophageal Neoplasms / genetics*
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Esophageal Neoplasms / pathology
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Esophageal Squamous Cell Carcinoma
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Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
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Gene Expression Regulation, Neoplastic
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Gene Knockdown Techniques
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Genes, Tumor Suppressor*
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Humans
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Lymphatic Metastasis
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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 / genetics
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MicroRNAs / physiology*
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Neoplasm Invasiveness / genetics
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Proto-Oncogene Proteins / biosynthesis
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Proto-Oncogene Proteins / genetics*
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Proto-Oncogene Proteins p21(ras)
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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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MIRN27 microRNA, human
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MicroRNAs
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Proto-Oncogene Proteins
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Extracellular Signal-Regulated MAP Kinases
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Proto-Oncogene Proteins p21(ras)
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ras Proteins