ArticleCell death discovery2022
LncRNA MEG3 up-regulates SIRT6 by ubiquitinating EZH2 and alleviates nonalcoholic fatty liver disease.
Article in Cell death discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- LncRNA and circRNA in Patients with Non-Alcoholic Fatty Liver Disease: A Systematic Review.Biomolecules · 2023Pooled it
- Unifying and unique roles of non-coding RNA biomarkers in liver and heart fibrosis.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Review
- Natural modulators of enhancer of zeste homolog 2 (EZH2): potential epigenetic regulators of aging-associated pathways.Biogerontology · 2026Review
- Studying the expression levels of LncRNA-MEG3 and miR-147b in the serum of psoriasis patients with and without dyslipidemia.Scientific reports · 2026Article
- METTL7B-stabilized lncRNA-MIR22HG to drive p53-mediated neuronal apoptosis via the ubiquitinating JARID2 in cerebral ischemia/reperfusion injury.Cell biology and toxicology · 2026Article
- miRNAs, lncRNAs, circRNAs and piRNAs in Nonalcoholic Fatty Liver Disease: Past, Present and Future.International journal of molecular sciences · 2025Review
- Extracellular vesicles in metabolic dysfunction-associated steatotic liver disease: From intercellular signaling to clinical translation.World journal of hepatology · 2025Review
- DNA-methylation-mediated silencing of lncRNA PP7080 promotes the progression of gastric cancer by regulating ANKRD1 expression.Translational oncology · 2025Article
- Review
- Long Non-Coding RNAs in Non-Alcoholic Fatty Liver Disease; Friends or Foes?Cell biochemistry and biophysics · 2025Review
- LncRNA Gm35585 transcriptionally activates the peroxidase EHHADH against diet-induced fatty liver.Experimental & molecular medicine · 2025Article
- Association between lipid accumulation product and non-alcoholic fatty liver disease with normal weight: a population-based study.Frontiers in medicine · 2025Article
- Longitudinal assessment of liver stiffness and risk factors for advanced fibrosis in adolescents with metabolic dysfunction-associated steatotic liver disease: a retrospective observational study.Frontiers in medicine · 2025Article
- Long noncoding RNAs in ubiquitination, protein degradation, and human diseases.Biochimica et biophysica acta. Gene regulatory mechanisms · 2024Review
- Mechanistic role of long non-coding RNAs in the pathogenesis of metabolic dysfunction-associated steatotic liver disease and fibrosis.eGastroenterology · 2024Article
- Impaired SUMOylation of FoxA1 promotes nonalcoholic fatty liver disease through down-regulation of Sirt6.Cell death & disease · 2024Article
- LncRNA MEG3 Restrains Hepatic Lipogenesis via the FOXO1 Signaling Pathway in HepG2 Cells.Cell biochemistry and biophysics · 2024Article
- Multifaceted roles of Meg3 in cellular senescence and atherosclerosis.Atherosclerosis · 2024Article
- Metabolic mechanisms orchestrated by Sirtuin family to modulate inflammatory responses.Frontiers in immunology · 2024Review
- LncRNA MEG3: Targeting the Molecular Mechanisms and Pathogenic causes of Metabolic Diseases.Current medicinal chemistry · 2024Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a global health threat. Here, we presented the significant role of a novel signaling axis comprising long non-coding RNA maternally expressed gene 3 (MEG3), enhancer of zeste homolog 2 (EZH2), and sirtuin 6 (SIRT6) in controlling lipid accumulation, inflammation, and the progression of NAFLD. Mice fed with high-fat diet (HFD) were established as in vitro and in vivo NAFLD models, respectively. Lipid accumulation was measured by oil red O staining and assays for triglycerides or cholesterol. Inflammation was examined by ELISA for pro-inflammatory cytokines. Gene expressions were examined by RT-qPCR or Western blot. Interactions between key signaling molecules were examined by combining expressional analysis, RNA immunoprecipitation, cycloheximide stability assay, co-immunoprecipitation, and chromatin immunoprecipitation. MEG3 level was reduced in FFA-challenged hepatocytes or liver from HFD-fed mice, and the reduction paralleled the severity of NAFLD in clinic. Overexpressing MEG3 suppressed FFA-induced lipid accumulation or inflammation in hepatocytes. By promoting the ubiquitination and degradation of EZH2, MEG3 upregulated SIRT6, an EZH2 target. SIRT6 essentially mediated the protective effects of MEG3 in hepatocytes. Consistently, overexpressing MEG3 alleviated HFD-induced NAFLD in vivo. By controlling the expressions of genes involved in lipid metabolism and inflammation, the MEG3/EZH2/SIRT6 axis significantly suppressed lipid accumulation and inflammation in vitro, and NAFLD development in vivo. Therefore, boosting MEG3 level may benefit the treatment of NAFLD.
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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.