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http://purl.uniprot.org/citations/24841200http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/24841200http://www.w3.org/2000/01/rdf-schema#comment"MicroRNA-200b (miR-200b) is a member of miR-200 family that has been found to inhibit cell migration and cancer metastasis; however, the underlying mechanism is not well understood. We previously reported that miR-200 expression is depleted in arsenic-transformed human bronchial epithelial cells with highly migratory and invasive characteristics, whereas stably re-expressing miR-200b strongly suppresses arsenic-transformed cell migration. This study was performed to investigate how miR-200b inhibits arsenic-transformed cell migration. We found that protein kinase Cα (PKCα) is significantly up-regulated in arsenic-transformed cells. Combining bioinformatics analysis with PKCα 3'-untranslated region vector luciferase reporter assays, we showed that PKCα is a direct target of miR-200b. Inhibiting PKCα activity or knocking down PKCα expression drastically reduced cell migration, phenocoping the inhibitory effect of overexpressing miR-200b. In contrast, forced expression of PKCα in miR-200b overexpressing cells impaired the inhibitory effect of miR-200b on cell migration. In addition, we also found a positive feedback loop between Wnt5b and PKCα in arsenic-transformed cells. Knocking down Wnt5b expression reduced phospho-PKC levels and cell migration; and knocking down PKCα expression decreased Wnt5b level and cell migration. Moreover, forced expression of PKCα increased Wnt5b and phospho-PKC levels and cell migration. Further mechanistic studies revealed that Rac1 is highly activated in arsenic-transformed cells and stably expressing miR-200b abolishes Rac1 activation changing actin cytoskeleton organization. Manipulating PKCα or Wnt5b expression levels significantly altered the level of active Rac1. Together, these findings indicate that miR-200b suppresses arsenic-transformed cell migration by targeting PKCα and Wnt5b-PKCα positive feedback loop and subsequently inhibiting Rac1 activation."xsd:string
http://purl.uniprot.org/citations/24841200http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m114.554246"xsd:string
http://purl.uniprot.org/citations/24841200http://purl.uniprot.org/core/author"Jiang Y."xsd:string
http://purl.uniprot.org/citations/24841200http://purl.uniprot.org/core/author"Wang Z."xsd:string
http://purl.uniprot.org/citations/24841200http://purl.uniprot.org/core/author"Yang C."xsd:string
http://purl.uniprot.org/citations/24841200http://purl.uniprot.org/core/author"Xiao H."xsd:string
http://purl.uniprot.org/citations/24841200http://purl.uniprot.org/core/author"Humphries B."xsd:string
http://purl.uniprot.org/citations/24841200http://purl.uniprot.org/core/date"2014"xsd:gYear
http://purl.uniprot.org/citations/24841200http://purl.uniprot.org/core/name"J Biol Chem"xsd:string
http://purl.uniprot.org/citations/24841200http://purl.uniprot.org/core/pages"18373-18386"xsd:string
http://purl.uniprot.org/citations/24841200http://purl.uniprot.org/core/title"MicroRNA-200b suppresses arsenic-transformed cell migration by targeting protein kinase Calpha and Wnt5b-protein kinase Calpha positive feedback loop and inhibiting Rac1 activation."xsd:string
http://purl.uniprot.org/citations/24841200http://purl.uniprot.org/core/volume"289"xsd:string
http://purl.uniprot.org/citations/24841200http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/24841200
http://purl.uniprot.org/citations/24841200http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/24841200
http://purl.uniprot.org/uniprot/#_A0A169TED2-mappedCitation-24841200http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24841200
http://purl.uniprot.org/uniprot/#_B0LPH5-mappedCitation-24841200http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24841200
http://purl.uniprot.org/uniprot/#_B7Z1Y5-mappedCitation-24841200http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24841200
http://purl.uniprot.org/uniprot/#_Q7Z727-mappedCitation-24841200http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24841200
http://purl.uniprot.org/uniprot/#_L7RSM7-mappedCitation-24841200http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24841200
http://purl.uniprot.org/uniprot/#_P17252-mappedCitation-24841200http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24841200
http://purl.uniprot.org/uniprot/#_Q2TSD3-mappedCitation-24841200http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24841200
http://purl.uniprot.org/uniprot/#_Q59G81-mappedCitation-24841200http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24841200
http://purl.uniprot.org/uniprot/#_Q59FI5-mappedCitation-24841200http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24841200
http://purl.uniprot.org/uniprot/#_Q9H1J7-mappedCitation-24841200http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24841200