title: Fascin regulates TLR4/PKC-mediated translational activation through miR-155 and miR-125b, which targets the 3' untranslated region of TNF-α mRNA.
abstract: Fascin is a well-known cytoskeletal regulatory protein that, as a substrate of protein kinase C (PKC), is involved in PKC-mediated translational regulation of TNF-α in macrophages stimulated with lipopolysaccharide (LPS). The regulatory effects of fascin targeted the 3'-untraslated region (UTR) of the TNF-α mRNA, and suppression of PKC activity or fascin expression resulted in specific blockage of the LPS-induced translational activation of the mRNA. In an effort to identify the molecular mechanism of this fascin-mediated translational regulation, the expression levels of micro-RNA (miRNA) after stimulation of the toll-like receptor 4 (TLR4) signaling pathways were analyzed in cells with down-regulation of fascin. The LPS-induced translation of TNF-α is known to be regulated by miR-155 and miR-125b, which have positive and negative effects, respectively. Interestingly, suppression of fascin expression reversed LPS-induced down-regulation of miR-125b and abolished the LPS-induced increase in miR-155. Furthermore, introduction of miR-155 precursor, blocking of miR-125b activity, or introduction of a mutation into the miR-125b binding site of the TNF-α 3'-UTR restored translational activation in cells with suppressed fascin expression. These data indicate that fascin regulates translation through miR-155 and miR-125b, which target 3' UTR in TNF-α mRNA.
authors.affiliation: School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University , Daegu , Republic of Korea and.
authors.forename: Jae-Kwan
authors.initials: JK
authors.lastname: Kim
authors.forename: Suk-Won
authors.initials: SW
authors.lastname: Jang
authors.forename: Kyoungho
authors.initials: K
authors.lastname: Suk
authors.forename: Won-Ha
authors.initials: WH
authors.lastname: Lee
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000502:physiology*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D002352:Carrier Proteins; D008070:Lipopolysaccharides; C531888:MIRN125 microRNA, human; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D008840:Microfilament Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C020324:fascin; D011493:Protein Kinase C
keywords: Fascin; TNF-α; miR-125b; miR-155; translational regulation