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Cited by 242Cholesterol and Lipid MetabolismMicroRNA in disease regulationLipoproteins and Cardiovascular Health

MicroRNA-758 Regulates Cholesterol Efflux Through Posttranscriptional Repression of ATP-Binding Cassette Transporter A1

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Ramirez, Cristina M., Dávalos, Alberto, Goedeke, Leigh, Salerno, Alessandro G., Warrier, Nikhil, Cirera-Salinas, Daniel, Suárez, Yajaira, Fernández-Hernando, Carlos·2011·Arteriosclerosis, Thrombosis, and Vascular Biology
DOI 10.1161/atvbaha.111.232066PMC PMC3298756
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Abstract

Objective—: The ATP-binding cassette transporter A1 (ABCA1) is a major regulator of macrophage cholesterol efflux and protects cells from excess intracellular cholesterol accumulation; however, the mechanism involved in posttranscriptional regulation of ABCA1 is poorly understood. We previously showed that microRNA-33 (miR-33) is 1 regulator. Here, we investigated the potential contribution of other microRNAs (miRNAs) to posttranscriptional regulation of ABCA1 and macrophage cholesterol efflux. Methods and Results—: We performed a bioinformatic analysis for identifying miRNA target prediction sites in ABCA1 gene and an unbiased genome-wide screen to identify miRNAs modulated by cholesterol excess in mouse peritoneal macrophages. Quantitative real-time reverse transcription–polymerase chain reaction confirmed that miR-758 is repressed in cholesterol-loaded macrophages. Under physiological conditions, high dietary fat excess in mice repressed miR-758 both in peritoneal macrophages and, to a lesser extent, in the liver. In mouse and human cells in vitro, miR-758 repressed the expression of ABCA1, and conversely, the inhibition of this miRNA by using anti-miR-758 increased ABCA1 expression. In mouse cells, miR-758 reduced cellular cholesterol efflux to apolipoprotein A1 (apoA1), and anti-miR-758 increased it. miR-758 directly targets the 3′-untranslated region of Abca1 as assessed by 3′-untranslated region luciferase reporter assays. Interestingly, miR-758 is highly expressed in the brain, where it also targets several genes involved in neurological functions, including Slc38a1, Ntm, Epha7 , and Mytl1 . Conclusion—: We identified miR-758 as a novel miRNA that posttranscriptionally controls ABCA1 levels in different cells and regulates macrophage cellular cholesterol efflux to apoA1, opening new avenues to increase apoA1 and raise high-density lipoprotein levels.

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Crossref · 10.1161/atvbaha.111.232066

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  • ABCA1 is redundantly targeted by miR-106b, miR-758, and miR-33 in the brain.

    “ABCA1 is redundantly targeted by miR-106b, miR-758, and miR-33 in the brain.”

    From MicroRNAs in brain cholesterol metabolism and their implications for Alzheimer's disease (2016) · cites this paper as [118]

    The Discussion (page unavailable) reports that miR-758 regulates ABCA1 in neuronal cells and is highly expressed in the brain. It also identifies miR-33 as another ABCA1 regulator, but does not establish its action in the brain. The paper does not identify miR-106b as an ABCA1 regulator, so it does not support the claim that all three redundantly target ABCA1 there. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • miR-758-5p is highly enriched in mouse brain.

    “miR-758-5p expression survey experiment indicated that it is highly enriched in mouse brain.”

    From MicroRNAs in brain cholesterol metabolism and their implications for Alzheimer's disease (2016) · cites this paper as [118]

    The Results section (‘miR-758 tissue and cellular expression and its regulation by plasma lipid levels in vivo’; page not provided) reports that miR-758 is particularly abundant in mouse brain and that whole-brain tissue has very high levels relative to other tissues. The copy calls it miR-758, however, and does not identify the measured form as miR-758-5p, so it does not establish the claim's strand-specific detail. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • miR-758-5p overexpression significantly decreases ABCA1 protein levels and cellular cholesterol efflux in cells, whereas inhibition of endogenous miR-758 causes opposite effects.

    “miR-758-5p overexpression significantly decreased ABCA1 protein levels and cellular cholesterol efflux in cells, whereas inhibition of endogenous miR-758 caused the opposite effects.”

    From MicroRNAs in brain cholesterol metabolism and their implications for Alzheimer's disease (2016) · cites this paper as [118]

    The Results section on neuroglioma cells reports that miR-758 overexpression decreased ABCA1 protein and cholesterol efflux to ApoA1, while inhibition increased both. Our copy calls the molecule miR-758, not miR-758-5p, so it does not establish the claim's strand-specific identification. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • miR-758-5p overexpression represses several genes involved in myelination, neuronal migration, and neurite outgrowth in human neuroglioma cells.

    “miR-758-5p overexpression repressed several genes involved in myelination, neuronal migration, and neurite outgrowth in human neuroglioma cells.”

    From MicroRNAs in brain cholesterol metabolism and their implications for Alzheimer's disease (2016) · cites this paper as [118]

    The Results section ('miR-758 controls cellular cholesterol efflux and other targets in neuroglioma cells'; page unavailable) reports that miR-758 overexpression significantly reduced several gene transcripts in H4 cells and identifies NTM as involved in neurite outgrowth. It does not identify the tested miRNA as miR-758-5p or establish that the repressed genes are involved in myelination and neuronal migration; MYT1L is listed as a predicted target but not among the genes whose expression fell. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

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Cites

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Cited by

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Authors
Ramirez, C. M., Dávalos, A., Goedeke, L., Salerno, A. G., Warrier, N., Cirera-Salinas, D., Suárez, Y., & Fernández-Hernando, C.
Affiliations
  • From the Departments of Medicine and Cell Biology, Leon H. Charney Division of Cardiology and the Marc and Ruti Bell Vascular Biology and Disease Program, New York University School of Medicine, New York, NY.
  • New York University (US)
ORCID
Venue
Arteriosclerosis, Thrombosis, and Vascular Biology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2011-11
Volume
31
Issue
11
Pages
2707-2714
ISSN
  • 1079-5642 (ISSN-L)
  • 1524-4636
DOI
10.1161/atvbaha.111.232066
PMC
PMC3298756
OpenAlex
W2107652148
Cited by
242
References
4
Citations by year
2026: 4 · 2025: 5 · 2024: 5 · 2023: 11 · 2022: 9 · 2021: 13 · 2020: 10 · 2019: 15 · 2018: 22 · 2017: 15 · 2016: 29 · 2015: 25 · 2014: 32 · 2013: 25 · 2012: 22
FWCI
25.89
Type
journal article
Language
en
Open access
Locations
  • Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Heart, Lung, and Blood Institute (R01HL106063, R01HL107953)
Topics
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Keywords
ABCA1, cholesterol efflux, macrophages, post-transcriptional regulation, 3' untranslated region, apolipoprotein A-I, high-density lipoprotein, peritoneal macrophages, miRNA target prediction, SLC38A1, nontuberculous mycobacteria, EphA7
MeSH terms
Animals, Astrocytes, Cell Line, Cholesterol, Humans, RNA Processing, Post-Transcriptional, Apolipoprotein A-I, Macrophages, Peritoneal, ATP-Binding Cassette Transporters, 3' Untranslated Regions, Hepatocytes, Models, Animal, MicroRNAs, Lipid Metabolism, Mice, ATP Binding Cassette Transporter 1

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