ArticleMolecular therapy. Nucleic acids2019
Control of LDL Uptake in Human Cells by Targeting the LDLR Regulatory Long Non-coding RNA BM450697.
Article in Molecular therapy. Nucleic acids, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 17 citations in OpenAlex.
- Overexpression of the lncRNA TUG1 regulates high-glucose-induced endocytic clearance dysfunction in HLSECs via the Wnt/β-catenin signaling pathway.European journal of medical research · 2025Article
- Long noncoding RNAs in familial hypercholesterolemia: biomarkers, therapeutics, and AI in precision medicine.Lipids in health and disease · 2025Review
- The Role of Selected lncRNAs in Lipid Metabolism and Cardiovascular Disease Risk.International journal of molecular sciences · 2024Review
- LncRNAs-circRNAs as Rising Epigenetic Binary Superstars in Regulating Lipid Metabolic Reprogramming of Cancers.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- Review
- Extracellular vesicles: The next generation in gene therapy delivery.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- Large-Scale CRISPR Screen of LDLR Pathogenic Variants.Research (Washington, D.C.) · 2023Article
- Mesenchymal Stem Cell exosome delivered Zinc Finger Protein activation of cystic fibrosis transmembrane conductance regulator.Journal of extracellular vesicles · 2021Article
- Long Non-Coding RNA Associated with Cholesterol Homeostasis and Its Involvement in Metabolic Diseases.International journal of molecular sciences · 2020Review
- Long Non-coding RNAs Mechanisms of Action in HIV-1 Modulation and the Identification of Novel Therapeutic Targets.Non-coding RNA · 2020Review
- Regulation of Glucose and Lipid Metabolism by Long Non-coding RNAs: Facts and Research Progress.Frontiers in endocrinology · 2020Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Hypercholesterolemia is a condition that is characterized by very high levels of cholesterol in the blood and is a major correlating factor with heart disease. Indeed, high levels of the low-density lipoprotein (LDL) have been causally linked to the development of atherosclerotic cardiovascular disease (ASCVD). A method to specifically reduce cholesterol in the blood in a long-term, stable manner could prove therapeutically relevant. Cholesterol is removed from the blood by the LDL receptor (LDLR) in the liver. Others and we have discovered that a long non-coding RNA (lncRNA; BM450697) functions as an endogenous epigenetic regulator of LDLR and that the repression of this lncRNA by the action of small interfering RNAs (siRNAs) results in the activation of LDLR. We found here, through the interrogation of two siRNAs that can target this lncRNA, both in a transcriptional and post-transcriptional manner, that BM450697 functions as a local scaffold for modulating LDLR transcription. Moreover, we found that conjugation of α-N-acetylgalactosamine (GalNAc) with two lncRNA-directed siRNAs allows for direct liver cell targeting of this lncRNA and functional enhanced uptake of cholesterol. Collectively, these data suggest that targeting the BM450697 lncRNA regulator of LDLR may result in a more specific, long-term, targeted approach to regulating cholesterol in the blood.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.