ArticleMolecular therapy : the journal of the American Society of Gene Therapy2024
Nuclear AGO2 promotes myocardial remodeling by activating ANKRD1 transcription in failing hearts.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 16 citations in OpenAlex.
- Argonaute 2 stabilization of microRNAs controls adult neurogenesis and oligodendrogenesis.Neural regeneration research · 2026Article
- Ankyrin Repeat Domain 1: A Key Regulatory Factor and Emerging Therapeutic Target in Heart Disease.Reviews in cardiovascular medicine · 2026Review
- Nuclear Proteome Map of Mouse Heart Chambers.Molecular & cellular proteomics : MCP · 2026Article
- Targeting the TRIM25-AGO2-miR-148b-5p-ABCC1 axis overcomes chemoresistance in non-small cell lung cancer.Cell death & disease · 2026Article
- Left bundle branch vs biventricular pacing: mechanistic insights from a canine model.European heart journal · 2026Article
- Structural insights into disease-associated mutations in the microRNA processing machinery.Experimental & molecular medicine · 2026Review
- ANKRD1 sustains a neurogenic BMSC niche and counters cognitive aging.International journal of oral science · 2026Article
- The roles of subcellular Argonaute 2 in cardiovascular diseases.Journal of translational internal medicine · 2025Article
- MYH6-Cre Insertion Accelerates Cardiac Phenotype in Dystrophic D2-mdx Mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- RBPMS inhibits bladder cancer metastasis by downregulating MYC pathway through alternative splicing of ANKRD10.Communications biology · 2025Article
- Research progress of ankyrin repeat domain 1 protein: an updated review.Cellular & molecular biology letters · 2024Review
- Metabolic and Proteomic Profiling of Coronary Microvascular Dysfunction: Insights from Rat Models.Biomolecules · 2024Article
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Authors and funding
12 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Heart failure (HF) is manifested by transcriptional and posttranscriptional reprogramming of critical genes. Multiple studies have revealed that microRNAs could translocate into subcellular organelles such as the nucleus to modify gene expression. However, the functional property of subcellular Argonaute2 (AGO2), the core member of the microRNA machinery, has remained elusive in HF. AGO2 was found to be localized in both the cytoplasm and nucleus of cardiomyocytes, and robustly increased in the failing hearts of patients and animal models. We demonstrated that nuclear AGO2 rather than cytosolic AGO2 overexpression by recombinant adeno-associated virus (serotype 9) with cardiomyocyte-specific troponin T promoter exacerbated the cardiac dysfunction in transverse aortic constriction (TAC)-operated mice. Mechanistically, nuclear AGO2 activates the transcription of ANKRD1, encoding ankyrin repeat domain-containing protein 1 (ANKRD1), which also has a dual function in the cytoplasm as part of the I-band of the sarcomere and in the nucleus as a transcriptional cofactor. Overexpression of nuclear ANKRD1 recaptured some key features of cardiac remodeling by inducing pathological MYH7 activation, whereas cytosolic ANKRD1 seemed cardioprotective. For clinical practice, we found ivermectin, an antiparasite drug, and ANPep, an ANKRD1 nuclear location signal mimetic peptide, were able to prevent ANKRD1 nuclear import, resulting in the improvement of cardiac performance in TAC-induced HF.
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