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Niespolo, C.* ; Johnston, J.M.* ; Deshmukh, S.R.* ; Satam, S. ; Shologu, Z.* ; Villacanas, O.* ; Sudbery, I.M.* ; Wilson, H.L.* ; Kiss-Toth, E.*

Tribbles-1 expression and its function to control inflammatory cytokines, including interleukin-8 levels are regulated by miRNAs in macrophages and prostate cancer cells.

Front. Immunol. 11:574046 (2020)
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The pseudokinase TRIB1 controls cell function in a range of contexts, by regulating MAP kinase activation and mediating protein degradation via the COP1 ubiquitin ligase. TRIB1 regulates polarization of macrophages and dysregulated Trib1 expression in murine models has been shown to alter atherosclerosis burden and adipose homeostasis. Recently, TRIB1 has also been implicated in the pathogenesis of prostate cancer, where it is often overexpressed, even in the absence of genetic amplification. Well described TRIB1 effectors include MAP kinases and C/EBP transcription factors, both in immune cells and in carcinogenesis. However, the mechanisms that regulate TRIB1 itself remain elusive. Here, we show that the long and conserved 3’untranslated region (3’UTR) of TRIB1 is targeted by miRNAs in macrophage and prostate cancer models. By using a systematic in silico analysis, we identified multiple “high confidence” miRNAs potentially binding to the 3’UTR of TRIB1 and report that miR-101-3p and miR-132-3p are direct regulators of TRIB1 expression and function. Binding of miR-101-3p and miR-132-3p to the 3’UTR of TRIB1 mRNA leads to an increased transcription and secretion of interleukin-8. Our data demonstrate that modulation of TRIB1 by miRNAs alters the inflammatory profile of both human macrophages and prostate cancer cells.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Inflammation ; Macrophages ; Mirna ; Prostate Cancer ; Tribbles; Epithelial-mesenchymal Transition; C/ebp-alpha; Invasion; Trib1; Proliferation; Metastasis; Migration; Targets; Overexpression; Morphogenesis
Sprache englisch
Veröffentlichungsjahr 2020
HGF-Berichtsjahr 2020
ISSN (print) / ISBN 1664-3224
e-ISSN 1664-3224
Zeitschrift Frontiers in Immunology
Quellenangaben Band: 11, Heft: , Seiten: , Artikelnummer: 574046 Supplement: ,
Verlag Frontiers
Verlagsort Avenue Du Tribunal Federal 34, Lausanne, Ch-1015, Switzerland
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Cancer (IDC)
POF Topic(s) 30201 - Metabolic Health
Forschungsfeld(er) Helmholtz Diabetes Center
PSP-Element(e) G-502591-001
Förderungen British Heart Foundation
European Marie Sklodowska Curie ITN Project TRAIN-TRIBBLES Research and Innovation Network
DOI 10.3389/fimmu.2020.574046
WOS ID WOS:000597296800001
Scopus ID 85097626354
Erfassungsdatum 2021-02-05
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