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Negative feedback regulation between microRNA let-7g and the oxLDL receptor LOX-1.
- Source :
-
Journal of cell science [J Cell Sci] 2011 Dec 01; Vol. 124 (Pt 23), pp. 4115-24. Date of Electronic Publication: 2011 Dec 01. - Publication Year :
- 2011
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Abstract
- Lectin-like oxidized LDL receptor-1 (LOX-1) is a surface scavenger receptor for oxidized low-density lipoprotein (oxLDL). Several transcription factors have been reported to regulate LOX-1 expression. MicroRNAs are small noncoding RNAs that control gene expression, but there have been no reports of LOX-1 expression being regulated by microRNAs. Because the microRNA let-7g has been predicted to bind to LOX-1 mRNA, we investigated whether let-7g can regulate LOX-1 expression. Our experiments first demonstrated that oxLDL can reduce let-7g expression. We later confirmed that there is a let-7g binding site on the 3'-untranslated region of LOX-1 mRNA. We showed that intracellular Ca(2+)-activated protein kinase C is involved in the oxLDL-LOX-1-let-7g pathway. Bioinformatics predicted that the let-7g promoter has a binding site for the transcriptional repressor OCT-1. We used a promoter assay and chromatin immunoprecipitation to confirm this binding. Consequently, knockdown of OCT-1 was found to increase let-7g expression. Transfection of let-7g inhibited oxLDL-induced LOX-1 and OCT-1 expression, cell proliferation and migration. Mice fed with a high-fat diet showed a decrease in let-7g and an increase in LOX-1 and OCT-1. A study on humans showed the serum levels of let-7g are lower in subjects with hypercholesterolemia compared with normal controls. Our findings identify a negative feedback regulation between let-7g and LOX-1, and indicate that let-7g could be a target to treat cardiovascular disease.
- Subjects :
- Animals
Aorta cytology
Aorta metabolism
Atherosclerosis metabolism
Atherosclerosis pathology
Cell Line
Cell Movement
Cell Proliferation
Humans
Hypercholesterolemia genetics
Hypercholesterolemia metabolism
Hypercholesterolemia pathology
Lipoproteins, LDL genetics
Mice
Mice, Inbred C57BL
MicroRNAs blood
MicroRNAs genetics
Mutagenesis, Site-Directed
Myocytes, Smooth Muscle cytology
Myocytes, Smooth Muscle metabolism
Primary Cell Culture
Scavenger Receptors, Class E genetics
Signal Transduction
Transfection
Wound Healing
Gene Expression Regulation
Lipoproteins, LDL metabolism
MicroRNAs metabolism
Scavenger Receptors, Class E metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1477-9137
- Volume :
- 124
- Issue :
- Pt 23
- Database :
- MEDLINE
- Journal :
- Journal of cell science
- Publication Type :
- Academic Journal
- Accession number :
- 22135361
- Full Text :
- https://doi.org/10.1242/jcs.092767