ArticleArteriosclerosis, thrombosis, and vascular biology2016
miRNA Targeting of Oxysterol-Binding Protein-Like 6 Regulates Cholesterol Trafficking and Efflux.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 73 citations in OpenAlex.
- OSBPL6 protects against demyelination and behavioral disorder via promoting cholesterol transport in oligodendrocyte.Journal of advanced research · 2026Article
- Mitochondrial Metabolic Biomarkers in Periodontitis: Discovery and Clinical Validation.International dental journal · 2026Article
- Oxysterol-binding protein-related protein 6 regulates neuronal morphology and migration of cerebellar granule cells during cerebellar developmentBiochemistry and biophysics reports · 2026Article
- Non-coding RNAs in lipid metabolism and their roles in atherosclerosis.Nature reviews. Cardiology · 2026Review
- Molecular Mechanisms Underlying Atherosclerosis and Current Advances in Targeted Therapeutics.International journal of molecular sciences · 2026Review
- Critical Role of microRNA-33a/b in Cardiovascular and Metabolic Disease: Molecular Mechanisms and Therapeutic Perspectives.Journal of atherosclerosis and thrombosis · 2026Review
- The microbiota-derived bile acid taurodeoxycholic acid improves hepatic cholesterol levels in mice with cancer cachexia.Gut microbes · 2025Article
- Proteomic Profiling of GLP-1-Mediated Cardioprotection in a Large Animal Model of Chronic Coronary Artery Disease.Medical research archives · 2025Article
- Genetic haplotypes inJournal for immunotherapy of cancer · 2025Article
- Single-Nuclei Transcriptome Profiling Reveals Intra-Tumoral Heterogeneity and Characterizes Tumor Microenvironment Architecture in a Murine Melanoma Model.International journal of molecular sciences · 2024Article
- Effects of miR-33 Deficiency on Metabolic and Cardiovascular Diseases: Implications for Therapeutic Intervention.International journal of molecular sciences · 2023Review
- Roles of Phosphatidylinositol 4-Phosphorylation in Non-vesicular Cholesterol Trafficking.Advances in experimental medicine and biology · 2023Article
- The involvement of oxysterol-binding protein related protein (ORP) 6 in the counter-transport of phosphatidylinositol-4-phosphate (PI4P) and phosphatidylserine (PS) in neurons.Biochemistry and biophysics reports · 2022Article
- The miR-23-27-24 cluster: an emerging target in NAFLD pathogenesis.Acta pharmacologica Sinica · 2022Review
- HDL and Lipid Metabolism.Advances in experimental medicine and biology · 2022Article
- Intertwined and Finely Balanced: Endoplasmic Reticulum Morphology, Dynamics, Function, and Diseases.Cells · 2021Review
- Article
- MicroRNA regulation of cholesterol metabolism.Annals of the New York Academy of Sciences · 2021Review
- MicroRNAs and Circular RNAs in Lipoprotein Metabolism.Current atherosclerosis reports · 2021Review
- miR-33 in cardiometabolic diseases: lessons learned from novel animal models and approaches.EMBO molecular medicine · 2021Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 3 countries.
Funding
Abstract
objectiveCholesterol homeostasis is fundamental to human health and is, thus, tightly regulated. MicroRNAs exert potent effects on biological pathways, including cholesterol metabolism, by repressing genes with related functions. We reasoned that this mode of pathway regulation could be exploited to identify novel genes involved in cholesterol homeostasis. APPROACH AND
resultsHere, we identify oxysterol-binding protein-like 6 (OSBPL6) as a novel target of 2 miRNA hubs regulating cholesterol homeostasis: miR-33 and miR-27b. Characterization of OSBPL6 revealed that it is transcriptionally regulated in macrophages and hepatocytes by liver X receptor and in response to cholesterol loading and in mice and nonhuman primates by Western diet feeding. OSBPL6 encodes the OSBPL-related protein 6 (ORP6), which contains dual membrane- and endoplasmic reticulum-targeting motifs. Subcellular localization studies showed that ORP6 is associated with the endolysosomal network and endoplasmic reticulum, suggesting a role for ORP6 in cholesterol trafficking between these compartments. Accordingly, knockdown of OSBPL6 results in aberrant clustering of endosomes and promotes the accumulation of free cholesterol in these structures, resulting in reduced cholesterol esterification at the endoplasmic reticulum. Conversely, ORP6 overexpression enhances cholesterol trafficking and efflux in macrophages and hepatocytes. Moreover, we show that hepatic expression of OSBPL6 is positively correlated with plasma levels of high-density lipoprotein cholesterol in a cohort of 200 healthy individuals, whereas its expression is reduced in human atherosclerotic plaques.
conclusionsThese studies identify ORP6 as a novel regulator of cholesterol trafficking that is part of the miR-33 and miR-27b target gene networks that contribute to the maintenance of cholesterol homeostasis.
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