ArticleMolecular therapy. Nucleic acids2019
Deletion of miR-126a Promotes Hepatic Aging and Inflammation in a Mouse Model of Cholestasis.
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 18 papers.
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Who cites it
18 citing papers in PubMed, 35 citations in OpenAlex.
- Using RNA therapeutics to promote healthy aging.Nature aging · 2025Review
- Senescence-like Phenotype After Chronic Exposure to Isoproterenol in Primary Quiescent Immune Cells.Biomolecules · 2024Article
- A defective splicing machinery promotes senescence through MDM4 alternative splicing.Aging cell · 2024Article
- Photobiomodulation Increases M2-Type Polarization of Macrophages by Inhibiting Versican Production After Spinal Cord Injury.Molecular neurobiology · 2024Article
- Molecular Morbidity Score-Can MicroRNAs Assess the Burden of Disease?International journal of molecular sciences · 2024Review
- Comprehensive analysis on subchondral bone marrow lesions of human osteoarthritis by integrating bulk and single-cell transcriptomes.BMC musculoskeletal disorders · 2023Article
- Efficient deletion of microRNAs using CRISPR/Cas9 with dual guide RNAs.Frontiers in molecular biosciences · 2023Article
- CRISPR/Cas9-Mediated Knockout of miR-130b Affects Mono- and Polyunsaturated Fatty Acid Content via PPARG-PGC1α Axis in Goat Mammary Epithelial Cells.International journal of molecular sciences · 2022Article
- Emerging Role of Non-Coding RNAs in Senescence.Frontiers in cell and developmental biology · 2022Review
- Interaction of NEP with G Protein Pathway Suppressor 2 Facilitates Influenza A Virus Replication by Weakening the Inhibition of GPS2 to RNA Synthesis and Ribonucleoprotein Assembly.Journal of virology · 2021Article
- Can Be miR-126-3p a Biomarker of Premature Aging? An Ex Vivo and In Vitro Study in Fabry Disease.Cells · 2021Article
- MicroRNA-126a-5p Exerts Neuroprotective Effects on Ischemic Stroke via Targeting NADPH Oxidase 2.Neuropsychiatric disease and treatment · 2021Article
- Versican: A Dynamic Regulator of the Extracellular Matrix.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2020Review
- MiR-126 Regulates Properties of SOX9Stem cell reports · 2020Article
- Transcriptome analysis of common and diverged circulating miRNAs between arterial and venous during aging.Aging · 2020Article
- Noncoding RNAs Controlling Telomere Homeostasis in Senescence and Aging.Trends in molecular medicine · 2020Review
- Versican-A Critical Extracellular Matrix Regulator of Immunity and Inflammation.Frontiers in immunology · 2020Review
- Downregulation of miR-486-5p Enhances the Anti-Tumor Effect of 5-Fluorouracil on Pancreatic Cancer Cells.OncoTargets and therapy · 2020Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
MicroRNAs (miRNAs) act as regulators of aging at the tissue or organism level or as regulators of cellular senescence. Targeted deletion of miR-126 in mice causes partial embryonic lethality, but its biological function in the liver is still largely unknown. Here, we deleted miR-126a, using the CRISPR/Cas9 system in vitro and in vivo. miR-126a was reduced in the aging livers, and disruption of miR-126a in bone mesenchymal stem cells (BMSCs) induced age-associated telomere shortening, DNA damage responses, and proinflammatory cytokines. Moreover, disruption of miR-126a in mice caused hepatocyte senescence, inflammation, and metabolism deficiency. In addition, disruption of miR-126a via BMSC transplantation aggravated the severity of liver defects induced by cholestasis compared with that in the functional miR-126a BMSC group. Mechanistically, we identified versican (VCAN) as a novel direct miR-126a-5p target that induces telomere shortening, BMSC senescence, and nuclear factor κB (NF-κB) pathway activation. This study identified aging-related reduced expression of miR-126a and promotion of its target VCAN as a key mechanism in the regulation of hepatic metabolic function during aging and hepatic damage by inducing NF-κB pathway activation, DNA repair function disorder, and telomere attrition. The findings indicate that miR-126a may be a drug target for the treatment of hepatic failure.
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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.