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Fascin regulates TLR4/PKC-mediated translational activation through miR-155 and miR-125b, which targets the 3' untranslated region of TNF-α mRNA.
Immunol Invest. 2015; 44(3):309-20.II

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+Show Affiliations

School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University , Daegu , Republic of Korea and.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25831081

Citation

Kim, Jae-Kwan, et al. "Fascin Regulates TLR4/PKC-mediated Translational Activation Through miR-155 and miR-125b, Which Targets the 3' Untranslated Region of TNF-α MRNA." Immunological Investigations, vol. 44, no. 3, 2015, pp. 309-20.
Kim JK, Jang SW, Suk K, et al. Fascin regulates TLR4/PKC-mediated translational activation through miR-155 and miR-125b, which targets the 3' untranslated region of TNF-α mRNA. Immunol Invest. 2015;44(3):309-20.
Kim, J. K., Jang, S. W., Suk, K., & Lee, W. H. (2015). Fascin regulates TLR4/PKC-mediated translational activation through miR-155 and miR-125b, which targets the 3' untranslated region of TNF-α mRNA. Immunological Investigations, 44(3), 309-20. https://doi.org/10.3109/08820139.2014.914533
Kim JK, et al. Fascin Regulates TLR4/PKC-mediated Translational Activation Through miR-155 and miR-125b, Which Targets the 3' Untranslated Region of TNF-α MRNA. Immunol Invest. 2015;44(3):309-20. PubMed PMID: 25831081.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fascin regulates TLR4/PKC-mediated translational activation through miR-155 and miR-125b, which targets the 3' untranslated region of TNF-α mRNA. AU - Kim,Jae-Kwan, AU - Jang,Suk-Won, AU - Suk,Kyoungho, AU - Lee,Won-Ha, Y1 - 2015/04/01/ PY - 2015/4/2/entrez PY - 2015/4/2/pubmed PY - 2016/1/16/medline KW - Fascin KW - TNF-α KW - miR-125b KW - miR-155 KW - translational regulation SP - 309 EP - 20 JF - Immunological investigations JO - Immunol Invest VL - 44 IS - 3 N2 - 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. SN - 1532-4311 UR - https://www.unboundmedicine.com/medline/citation/25831081/Fascin_regulates_TLR4/PKC_mediated_translational_activation_through_miR_155_and_miR_125b_which_targets_the_3'_untranslated_region_of_TNF_α_mRNA_ DB - PRIME DP - Unbound Medicine ER -