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MicroRNAs modulate the noncanonical NF-κB pathway by regulating IKKα expression during macrophage differentiation

MicroRNAs are key regulators in many biological processes including cell differentiation. Here we show that during human monocyte-macrophage differentiation, the expression of the microRNAs miR-223, miR-15a, and miR-16 is dramatically decreased, leading to increased expression of the serine-threonin...

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Detalles Bibliográficos
Autores principales: Li, Tao, Morgan, Michael J., Choksi, Swati, Zhang, Yan, Kim, You-Sun, Liu, Zheng-gang
Formato: Texto
Lenguaje:English
Publicado: 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2926307/
https://www.ncbi.nlm.nih.gov/pubmed/20711193
http://dx.doi.org/10.1038/ni.1918
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author Li, Tao
Morgan, Michael J.
Choksi, Swati
Zhang, Yan
Kim, You-Sun
Liu, Zheng-gang
author_facet Li, Tao
Morgan, Michael J.
Choksi, Swati
Zhang, Yan
Kim, You-Sun
Liu, Zheng-gang
author_sort Li, Tao
collection PubMed
description MicroRNAs are key regulators in many biological processes including cell differentiation. Here we show that during human monocyte-macrophage differentiation, the expression of the microRNAs miR-223, miR-15a, and miR-16 is dramatically decreased, leading to increased expression of the serine-threonine kinase IKKα in macrophages. In macrophages, higher IKKα expression in conjunction with stabilization of the kinase NIK induces elevated p52. Due to low RelB transcription factor expression in untreated macrophages, high p52 expression represses the basal level of both canonical and noncanonical NF-κB target genes. However, proinflammatory stimuli in macrophages result in greater induction of noncanonical NF-κB target genes. Thus a decrease in certain microRNAs likely prevents macrophage hyperaction yet primes the macrophage for certain responses to proinflammatory stimuli.
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spelling pubmed-29263072011-03-01 MicroRNAs modulate the noncanonical NF-κB pathway by regulating IKKα expression during macrophage differentiation Li, Tao Morgan, Michael J. Choksi, Swati Zhang, Yan Kim, You-Sun Liu, Zheng-gang Nat Immunol Article MicroRNAs are key regulators in many biological processes including cell differentiation. Here we show that during human monocyte-macrophage differentiation, the expression of the microRNAs miR-223, miR-15a, and miR-16 is dramatically decreased, leading to increased expression of the serine-threonine kinase IKKα in macrophages. In macrophages, higher IKKα expression in conjunction with stabilization of the kinase NIK induces elevated p52. Due to low RelB transcription factor expression in untreated macrophages, high p52 expression represses the basal level of both canonical and noncanonical NF-κB target genes. However, proinflammatory stimuli in macrophages result in greater induction of noncanonical NF-κB target genes. Thus a decrease in certain microRNAs likely prevents macrophage hyperaction yet primes the macrophage for certain responses to proinflammatory stimuli. 2010-08-15 2010-09 /pmc/articles/PMC2926307/ /pubmed/20711193 http://dx.doi.org/10.1038/ni.1918 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Li, Tao
Morgan, Michael J.
Choksi, Swati
Zhang, Yan
Kim, You-Sun
Liu, Zheng-gang
MicroRNAs modulate the noncanonical NF-κB pathway by regulating IKKα expression during macrophage differentiation
title MicroRNAs modulate the noncanonical NF-κB pathway by regulating IKKα expression during macrophage differentiation
title_full MicroRNAs modulate the noncanonical NF-κB pathway by regulating IKKα expression during macrophage differentiation
title_fullStr MicroRNAs modulate the noncanonical NF-κB pathway by regulating IKKα expression during macrophage differentiation
title_full_unstemmed MicroRNAs modulate the noncanonical NF-κB pathway by regulating IKKα expression during macrophage differentiation
title_short MicroRNAs modulate the noncanonical NF-κB pathway by regulating IKKα expression during macrophage differentiation
title_sort micrornas modulate the noncanonical nf-κb pathway by regulating ikkα expression during macrophage differentiation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2926307/
https://www.ncbi.nlm.nih.gov/pubmed/20711193
http://dx.doi.org/10.1038/ni.1918
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