ArticleAtherosclerosis2015
MicroRNA-27a decreases the level and efficiency of the LDL receptor and contributes to the dysregulation of cholesterol homeostasis.
Article in Atherosclerosis, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 99 citations in OpenAlex.
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- The Impact of IGFBP6 Knockdown on Cholesterol Metabolism in Breast Cancer Cells.Current medicinal chemistry · 2026Article
- Regulatory mechanisms of hepatocyte PCSK9 expression: translating mechanistic insights into potential nutraceuticals.Chinese medicine · 2025Review
- Involvement of miRNAs in the Cluster of Metabolic Factors of MetS: Nutrition-Genome-MetS Axis.Journal of clinical medicine · 2025Review
- Methionine Metabolism Dictates PCSK9 Expression and Antitumor Potency of PD-1 Blockade in MSS Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Pathways and Molecular Mechanisms Governing LDL Receptor Regulation.Circulation research · 2025Review
- Non-Coding RNA Involved in the Pathogenesis of Atherosclerosis-A Narrative Review.Diagnostics (Basel, Switzerland) · 2024Review
- Exploring the versatility of miRNA-128: a comprehensive review on its role as a biomarker and therapeutic target in clinical pathways.Molecular biology reports · 2024Review
- Specific circulating miRNAs are associated with plasma lipids in a healthy American cohort.Physiological genomics · 2024Article
- MiR-99a-5p up-regulates LDLR and functionally enhances LDL-C uptake via suppressing PCSK9 expression in human hepatocytes.Frontiers in genetics · 2024Article
- Evaluation of miRNA-27a/b expression in patients with familial hypercholesterolemia.Archives of medical science : AMS · 2024Article
- Functional Analysis of 3'UTR Variants at theHuman mutation · 2024Article
- The Link between miRNAs and PCKS9 in Atherosclerosis.Current medicinal chemistry · 2024Review
- Article
- The effect of PCSK9 immunization on the hepatic level of microRNAs associated with the PCSK9/LDLR pathway.Archives of medical science : AMS · 2023Article
- The potential role of miR-27a and miR-320a in metabolic syndrome in obese Egyptian females.Journal, genetic engineering & biotechnology · 2022Article
- The miR-23-27-24 cluster: an emerging target in NAFLD pathogenesis.Acta pharmacologica Sinica · 2022Review
- Review
- The Compatibility of Alisma and Atractylodes Affects the Biological Behaviours of VSMCs by Inhibiting the miR-128-5p/p21 Gene.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Regulatory Non-Coding RNAs in Familial Hypercholesterolemia, Theranostic Applications.Frontiers in cell and developmental biology · 2022Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
rationaleA strong risk factor for atherosclerosis- the leading cause of heart attacks and strokes- is the elevation of low-density lipoprotein cholesterol (LDL-C) in blood. The LDL receptor (LDLR) is the primary pathway for LDL-C removal from circulation, and their levels are increased by statins -the main treatment for high blood LDL-C. However, statins have low efficiency because they also increase PCSK9 which targets LDLR for degradation. Since microRNAs have recently emerged as key regulators of cholesterol homeostasis, our aim was to identify potential microRNA-based therapeutics to decrease blood LDL-C and prevent atherosclerosis. METHODS AND
resultsWe over expressed and knocked down miR-27a in HepG2 cells to assess its effect on the expression of key players in the LDLR pathway using PCR Arrays, Elisas, and Western blots. We found that miR-27a decreases LDLR levels by 40% not only through a direct binding to its 3' untranslated region but also indirectly by inducing a 3-fold increase in PCSK9, which enhances LDLR degradation. Interestingly, miR-27a also directly decreases LRP6 and LDLRAP1, two other key players in the LDLR pathway that are required for efficient endocytosis of the LDLR-LDL-C complex in the liver. The inhibition of miR-27a using lock nucleic acids induced a 70% increase in LDLR levels and, therefore, it would be a more efficient treatment for hypercholesterolemia because of its desirable effects not only on LDLR but also on PCSK9.
conclusionThe results presented here provide evidence supporting the potential of miR-27a as a novel therapeutic target for the prevention of atherosclerosis.
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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.