Negative feedback regulation between microRNA let-7g and the oxLDL receptor LOX-1

Ku Chung Chen, I. Chung Hsieh, Edward Hsi, Yung Song Wang, Chia Yen Dai, Wen Wen Chou, Suh Hang Hank Juo

Research output: Contribution to journalArticle

70 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4115-4124
Number of pages10
JournalJournal of Cell Science
Volume124
Issue number23
DOIs
Publication statusPublished - Dec 2011
Externally publishedYes

Fingerprint

Oxidized LDL Receptors
LDL Receptors
MicroRNAs
LDL Lipoproteins
Binding Sites
oxidized low density lipoprotein
Scavenger Receptors
Small Untranslated RNA
Messenger RNA
Chromatin Immunoprecipitation
3' Untranslated Regions
High Fat Diet
Hypercholesterolemia
Computational Biology
Lectins
Protein Kinase C
Cell Movement
Transfection

Keywords

  • Atherosclerosis
  • Let-7g
  • LOX-1
  • Microrna
  • OxLDL

ASJC Scopus subject areas

  • Cell Biology

Cite this

Chen, K. C., Hsieh, I. C., Hsi, E., Wang, Y. S., Dai, C. Y., Chou, W. W., & Juo, S. H. H. (2011). Negative feedback regulation between microRNA let-7g and the oxLDL receptor LOX-1. Journal of Cell Science, 124(23), 4115-4124. https://doi.org/10.1242/jcs.092767

Negative feedback regulation between microRNA let-7g and the oxLDL receptor LOX-1. / Chen, Ku Chung; Hsieh, I. Chung; Hsi, Edward; Wang, Yung Song; Dai, Chia Yen; Chou, Wen Wen; Juo, Suh Hang Hank.

In: Journal of Cell Science, Vol. 124, No. 23, 12.2011, p. 4115-4124.

Research output: Contribution to journalArticle

Chen, KC, Hsieh, IC, Hsi, E, Wang, YS, Dai, CY, Chou, WW & Juo, SHH 2011, 'Negative feedback regulation between microRNA let-7g and the oxLDL receptor LOX-1', Journal of Cell Science, vol. 124, no. 23, pp. 4115-4124. https://doi.org/10.1242/jcs.092767
Chen, Ku Chung ; Hsieh, I. Chung ; Hsi, Edward ; Wang, Yung Song ; Dai, Chia Yen ; Chou, Wen Wen ; Juo, Suh Hang Hank. / Negative feedback regulation between microRNA let-7g and the oxLDL receptor LOX-1. In: Journal of Cell Science. 2011 ; Vol. 124, No. 23. pp. 4115-4124.
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