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Tribbles-1 Expression and Its Function to Control Inflammatory Cytokines, Including Interleukin-8 Levels are Regulated by miRNAs in Macrophages and Prostate Cancer Cells

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 atheroscle...

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Autores principales: Niespolo, Chiara, Johnston, Jessica M., Deshmukh, Sumeet R., Satam, Swapna, Shologu, Ziyanda, Villacanas, Oscar, Sudbery, Ian M., Wilson, Heather L., Kiss-Toth, Endre
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728618/
https://www.ncbi.nlm.nih.gov/pubmed/33329538
http://dx.doi.org/10.3389/fimmu.2020.574046
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author Niespolo, Chiara
Johnston, Jessica M.
Deshmukh, Sumeet R.
Satam, Swapna
Shologu, Ziyanda
Villacanas, Oscar
Sudbery, Ian M.
Wilson, Heather L.
Kiss-Toth, Endre
author_facet Niespolo, Chiara
Johnston, Jessica M.
Deshmukh, Sumeet R.
Satam, Swapna
Shologu, Ziyanda
Villacanas, Oscar
Sudbery, Ian M.
Wilson, Heather L.
Kiss-Toth, Endre
author_sort Niespolo, Chiara
collection PubMed
description 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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spelling pubmed-77286182020-12-15 Tribbles-1 Expression and Its Function to Control Inflammatory Cytokines, Including Interleukin-8 Levels are Regulated by miRNAs in Macrophages and Prostate Cancer Cells Niespolo, Chiara Johnston, Jessica M. Deshmukh, Sumeet R. Satam, Swapna Shologu, Ziyanda Villacanas, Oscar Sudbery, Ian M. Wilson, Heather L. Kiss-Toth, Endre Front Immunol Immunology 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. Frontiers Media S.A. 2020-11-27 /pmc/articles/PMC7728618/ /pubmed/33329538 http://dx.doi.org/10.3389/fimmu.2020.574046 Text en Copyright © 2020 Niespolo, Johnston, Deshmukh, Satam, Shologu, Villacanas, Sudbery, Wilson and Kiss-Toth http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Niespolo, Chiara
Johnston, Jessica M.
Deshmukh, Sumeet R.
Satam, Swapna
Shologu, Ziyanda
Villacanas, Oscar
Sudbery, Ian M.
Wilson, Heather L.
Kiss-Toth, Endre
Tribbles-1 Expression and Its Function to Control Inflammatory Cytokines, Including Interleukin-8 Levels are Regulated by miRNAs in Macrophages and Prostate Cancer Cells
title Tribbles-1 Expression and Its Function to Control Inflammatory Cytokines, Including Interleukin-8 Levels are Regulated by miRNAs in Macrophages and Prostate Cancer Cells
title_full Tribbles-1 Expression and Its Function to Control Inflammatory Cytokines, Including Interleukin-8 Levels are Regulated by miRNAs in Macrophages and Prostate Cancer Cells
title_fullStr Tribbles-1 Expression and Its Function to Control Inflammatory Cytokines, Including Interleukin-8 Levels are Regulated by miRNAs in Macrophages and Prostate Cancer Cells
title_full_unstemmed Tribbles-1 Expression and Its Function to Control Inflammatory Cytokines, Including Interleukin-8 Levels are Regulated by miRNAs in Macrophages and Prostate Cancer Cells
title_short Tribbles-1 Expression and Its Function to Control Inflammatory Cytokines, Including Interleukin-8 Levels are Regulated by miRNAs in Macrophages and Prostate Cancer Cells
title_sort tribbles-1 expression and its function to control inflammatory cytokines, including interleukin-8 levels are regulated by mirnas in macrophages and prostate cancer cells
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728618/
https://www.ncbi.nlm.nih.gov/pubmed/33329538
http://dx.doi.org/10.3389/fimmu.2020.574046
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