ArticleMolecular therapy. Nucleic acids2015
In Vitro and In Vivo Modulation of Alternative Splicing by the Biguanide Metformin.
Article in Molecular therapy. Nucleic acids, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 79 citations in OpenAlex.
- Treatment updates in myotonic disorders.Journal of neurology · 2026Review
- RNA-Binding Motif Protein 3 as a Therapeutic and Prognostic Target for Drug Discovery.Current issues in molecular biology · 2026Review
- Metformin improves RAN protein pathology, alternative splicing, and behavioral phenotypes in SCA8 mice.Life science alliance · 2026Article
- Disruptions of cell signaling pathways in myotonic dystrophy type 1 skeletal muscle, their pathogenic impact, and potential for combinatorial therapeutics.The Journal of biological chemistry · 2026Review
- Alternative Splicing Regulation in Metabolic Disorders.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025Review
- Multisystem Symptoms in Myotonic Dystrophy Type 1: A Management and Therapeutic Perspective.International journal of molecular sciences · 2025Review
- The role of CNBP in brain atrophy and its targeting in myotonic dystrophy type 2.Human molecular genetics · 2025Article
- Downregulation of the Unfolded Protein Response Links Metformin Treatment to Good Clinical Outcomes in Colorectal Cancer Patients.Current oncology (Toronto, Ont.) · 2025Article
- Therapeutic advances in type 1 myotonic dystrophy complicated with type 2 diabetes mellitus.Frontiers in neurology · 2025Review
- Therapeutic modulation of protein RBM3 for ischemic stroke treatment.Frontiers in pharmacology · 2025Review
- AntimiR treatment corrects myotonic dystrophy primary cell defects across several CTG repeat expansions with a dual mechanism of action.Science advances · 2024Article
- Investigation of Glucose Metabolism by Continuous Glucose Monitoring and Validation of Dipeptidyl Peptidase 4 Inhibitor Use in Patients with Myotonic Dystrophy Type 1.Journal of clinical medicine · 2024Article
- HNRNPH1 regulates the neuroprotective cold-shock protein RBM3 expression through poison exon exclusion.The EMBO journal · 2023Article
- Senescent immune cells accumulation promotes brown adipose tissue dysfunction during aging.Nature communications · 2023Article
- Vorinostat Improves Myotonic Dystrophy Type 1 Splicing Abnormalities in DM1 Muscle Cell Lines and Skeletal Muscle from a DM1 Mouse Model.International journal of molecular sciences · 2023Article
- Pluripotent Stem Cells in Disease Modeling and Drug Discovery for Myotonic Dystrophy Type 1.Cells · 2023Review
- Metformin Treatment Modulates Long Non-Coding RNA Isoforms Expression in Human Cells.Non-coding RNA · 2022Article
- Development of Therapeutic Approaches for Myotonic Dystrophies Type 1 and Type 2.International journal of molecular sciences · 2022Review
- Skeletal Muscle Cells Derived from Induced Pluripotent Stem Cells: A Platform for Limb Girdle Muscular Dystrophies.Biomedicines · 2022Article
- Targeting Myotonic Dystrophy Type 1 with Metformin.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
20 authors at 13 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Major physiological changes are governed by alternative splicing of RNA, and its misregulation may lead to specific diseases. With the use of a genome-wide approach, we show here that this splicing step can be modified by medication and demonstrate the effects of the biguanide metformin, on alternative splicing. The mechanism of action involves AMPK activation and downregulation of the RBM3 RNA-binding protein. The effects of metformin treatment were tested on myotonic dystrophy type I (DM1), a multisystemic disease considered to be a spliceopathy. We show that this drug promotes a corrective effect on several splicing defects associated with DM1 in derivatives of human embryonic stem cells carrying the causal mutation of DM1 as well as in primary myoblasts derived from patients. The biological effects of metformin were shown to be compatible with typical therapeutic dosages in a clinical investigation involving diabetic patients. The drug appears to act as a modifier of alternative splicing of a subset of genes and may therefore have novel therapeutic potential for many more diseases besides those directly linked to defective alternative splicing.
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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.