Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 286, Issue 29, Pages 25531-25539Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M111.256206
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- Science Foundation Ireland
- Health Research Board Ireland [PhD/20007/9]
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Toll-like receptors (TLRs) modulate the expression of multiple microRNAs (miRNAs). Here, we report the down-regulation of miR-107 by TLR4 in multiple cell types. The miR-107 sequence occurs in an intron within the sequence encoding the gene for pantothenate kinase 1 alpha (PanK1 alpha), which is regulated by the transcription factor peroxisome proliferator-activating receptor alpha (PPAR-alpha). PanK1 alpha is also decreased in response to lipopolysaccharide (LPS). The effect on both miR-107 and PanK1 alpha is consistent with a decrease in PPAR-alpha expression. We have found that the putative miR-107 target cyclin-dependent kinase 6 (CDK6) expression is increased by TLR4 as a result of the decrease in miR-107. This effect is required for increased adhesion of macrophages in response to LPS, and CDK6-deficient mice are resistant to the lethal effect of LPS. We have therefore identified a mechanism for LPS signaling which involves a decrease in miR-107 leading to an increase in CDK6.
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