ArticleActa pharmacologica Sinica2017
Dicer1/miR-29/HMGCR axis contributes to hepatic free cholesterol accumulation in mouse non-alcoholic steatohepatitis.
Article in Acta pharmacologica Sinica, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 48 citations in OpenAlex.
- LncRNA TUG1 promotes hepatic lipid accumulation by targeting the miR-29a-3p/SREBP-2/HMGCR axis in MAFLD.Functional & integrative genomics · 2026Article
- Long noncoding RNAs in familial hypercholesterolemia: biomarkers, therapeutics, and AI in precision medicine.Lipids in health and disease · 2025Review
- Mechanism of Metabolic Dysfunction-associated Steatotic Liver Disease: Important role of lipid metabolism.Journal of clinical and translational hepatology · 2024Review
- Stress-Induced Immunosuppression Inhibits Regional Immune Responses in Chicken Adipose Tissue Partially through Suppressing T Cells by Up-Regulating Steroid Metabolism.Animals : an open access journal from MDPI · 2024Article
- Evolving Diagnostic and Treatment Strategies for Pediatric CNS Tumors: The Impact of Lipid Metabolism.Biomedicines · 2023Review
- Epidemiologic, Genetic, Pathogenic, Metabolic, Epigenetic Aspects Involved in NASH-HCC: Current Therapeutic Strategies.Cancers · 2022Review
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- Current Options and Future Directions for NAFLD and NASH Treatment.International journal of molecular sciences · 2021Review
- Improvement of hyperlipidemia by aerobic exercise in mice through a regulatory effect of miR-21a-5p on its target genes.Scientific reports · 2021Article
- Effect of statins on lipid metabolism-related microRNA expression in HepG2 cells.Pharmacological reports : PR · 2021Article
- MicroRNAs in the Pathogenesis of Nonalcoholic Fatty Liver Disease.International journal of biological sciences · 2021Review
- Synergistic Effect of Statins and Abiraterone Acetate on the Growth Inhibition of NeuroblastomaFrontiers in oncology · 2021Article
- miR-29a Modulates GSK3β/SIRT1-Linked Mitochondrial Proteostatic Stress to Ameliorate Mouse Non-Alcoholic Steatohepatitis.International journal of molecular sciences · 2020Article
- Pervasive Small RNAs in Cardiometabolic Research: Great Potential Accompanied by Biological and Technical Barriers.Diabetes · 2020Article
- Review
- Compounds that modulate AMPK activity and hepatic steatosis impact the biosynthesis of microRNAs required to maintain lipid homeostasis in hepatocytes.EBioMedicine · 2020Article
- Integrated microRNA and proteome analysis reveal a regulatory module in hepatic lipid metabolism disorders in mice with subclinical hypothyroidism.Experimental and therapeutic medicine · 2020Article
- Disturbances in Cholesterol Homeostasis and Non-alcoholic Fatty Liver Diseases.Frontiers in medicine · 2020Review
- The Crosstalk of miRNA and Oxidative Stress in the Liver: From Physiology to Pathology and Clinical Implications.International journal of molecular sciences · 2019Review
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dicer1 is an enzyme essential for microRNA (miRNA) maturation. The loss of miRNAs resulted from Dicer1 deficiency greatly contributes to the progression of many diseases, including lipid dysregulation, but its role in hepatic accumulation of free cholesterol (FC) that is critical in the development of non-alcoholic steatohepatitis (NASH) remains elusive. In this study, we used the liver-specific Dicer1-knockout mice to identify the miRNAs involved in hepatic FC accumulation. In a widely used dietary NASH model, mice were fed a methionine-choline-deficient (MCD) diet for 3 weeks, which resulted in significant increase in hepatic FC levels as well as decrease of Dicer1 mRNA levels in livers. The liver-specific Dicer1-knockout induced hepatic FC accumulation at 5-6 weeks, accompanied by increased mRNA and protein levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), a rate-limiting enzyme of cholesterol synthesis in livers. Eleven predicted miRNAs were screened, revealing that miR-29a/b/c significantly suppressed HMGCR expression by targeting the HMGCR mRNA 3'-UTR. Overexpression of miR-29a in SMMC-7721 cells, a steatosis hepatic cell model, significantly decreased HMGCR expression and the FC level. Furthermore, the expression levels of miR-29a were inversely correlated with HMGCR expression levels in the MCD diet mouse model in vivo and in 2 steatosis hepatic cell models (SMMC-7721 and HL-7702 cells) in vitro. Our results show that Dicer1/miR-29/HMGCR axis contributes to hepatic free cholesterol accumulation in mouse NASH, and miR-29 may serve as an important regulator of hepatic cholesterol homeostasis. Thus, miR-29a could be utilized as a potential therapeutic target for the treatment of non-alcoholic fatty liver disease as well as for other liver diseases associated with FC accumulation.
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