ArticlePloS one2014
MiR-21 simultaneously regulates ERK1 signaling in HSC activation and hepatocyte EMT in hepatic fibrosis.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 2 of them syntheses that pooled it.
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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
61 citing papers in PubMed, 2 syntheses or guidelines pooled it, 104 citations in OpenAlex.
- Investigating microRNAs to Explain the Link between Cholesterol Metabolism and NAFLD in Humans: A Systematic Review.Nutrients · 2022Pooled it
- Differentially Expressed miRNAs in Ulcerative Colitis and Crohn's Disease.Frontiers in immunology · 2022Pooled it
- Unifying and unique roles of non-coding RNA biomarkers in liver and heart fibrosis.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Review
- Predictive Analysis on the Mechanism of Dendrobium officinale Polysaccharides in Treating Hepatic Fibrosis via Network Pharmacology and Molecular Docking.BioMed research international · 2026Article
- Expression Analysis of Circulating miR-21, miR-34a and miR-122 and Redox Status Markers in Metabolic Dysfunction-Associated Steatotic Liver Disease Patients with and Without Type 2 Diabetes.International journal of molecular sciences · 2025Article
- Nicotinamide Adenine Dinucleotide Phosphate Oxidases and Metabolic Dysfunction-Associated Steatotic Liver Disease.Antioxidants (Basel, Switzerland) · 2025Review
- MicroRNA signatures in the pathogenesis and therapy of inflammatory bowel disease.Clinical and experimental medicine · 2024Review
- Regulation of Hepatocellular Carcinoma Epithelial-Mesenchymal Transition Mechanism and Targeted Therapeutic Approaches.Advances in experimental medicine and biology · 2024Review
- MicroRNAs in Anticancer Drugs Hepatotoxicity: From Pathogenic Mechanism and Early Diagnosis to Therapeutic Targeting by Natural Products.Current pharmaceutical biotechnology · 2024Review
- [Lithocholic acid decreases mRNA stability of nuclear receptor PPARNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023Article
- The role of microRNAs in the modulation of cancer-associated fibroblasts activity during pancreatic cancer pathogenesis.Journal of physiology and biochemistry · 2023Review
- FDRdb: a manually curated database of fibrotic disease-associated RNAome and high-throughput datasets.Database : the journal of biological databases and curation · 2022Article
- The Implications of Noncoding RNAs in the Evolution and Progression of Nonalcoholic Fatty Liver Disease (NAFLD)-Related HCC.International journal of molecular sciences · 2022Review
- Western diet-induced shifts in the maternal microbiome are associated with altered microRNA expression in baboon placenta and fetal liver.Frontiers in clinical diabetes and healthcare · 2022Article
- Mir-21 Suppression Promotes Mouse Hepatocarcinogenesis.Cancers · 2021Article
- Review
- Non-coding RNA crosstalk with nuclear receptors in liver disease.Biochimica et biophysica acta. Molecular basis of disease · 2021Review
- 5-methoxytryptophan alleviates liver fibrosis by modulating FOXO3a/miR-21/ATG5 signaling pathway mediated autophagy.Cell cycle (Georgetown, Tex.) · 2021Article
- Predicting Nonalcoholic Fatty Liver Disease through a Panel of Plasma Biomarkers and MicroRNAs in Female West Virginia Population.International journal of molecular sciences · 2020Article
- Nutrition and Genetics in NAFLD: The Perfect Binomium.International journal of molecular sciences · 2020Review
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMicroRNA-21 (miR-21) plays an important role in the pathogenesis and progression of liver fibrosis. Here, we determined the serum and hepatic content of miR-21 in patients with liver cirrhosis and rats with dimethylnitrosamine-induced hepatic cirrhosis and examined the effects of miR-21 on SPRY2 and HNF4α in modulating ERK1 signaling in hepatic stellate cells (HSCs) and epithelial-mesenchymal transition (EMT) of hepatocytes.
methodsQuantitative RT-PCR was used to determine miR-21 and the expression of SPRY2, HNF4α and other genes. Immunoblotting assay was carried out to examine the expression of relevant proteins. Luciferase reporter assay was performed to assess the effects of miR-21 on its predicted target genes SPRY2 and HNF4α. Primary HSCs and hepatocytes were treated with miR-21 mimics/inhibitors or appropriate adenoviral vectors to examine the relation between miR-21 and SPRY2 or HNF4α.
resultsThe serum and hepatic content of miR-21 was significantly higher in cirrhotic patients and rats. SPRY2 and HNF4α mRNA levels were markedly lower in the cirrhotic liver. MiR-21 overexpression was associated with enhanced ERK1 signaling and EMT in liver fibrosis. Luciferase assay revealed suppressed SPRY2 and HNF4α expression by miR-21. Ectopic miR-21 stimulated ERK1 signaling in HSCs and induced hepatocyte EMT by targeting SPRY2 or HNF4α. Downregulating miR-21 suppressed ERK1 signaling, inhibited HSC activation, and blocked EMT in TGFβ1-treated hepatocytes.
conclusionsMiR-21 modulates ERK1 signaling and EMT in liver fibrosis by regulating SPRY2 and HNF4α expression. MiR-21 may serve as a potentially biomarker as well as intervention target for hepatic cirrhosis.
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Registered trials
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