ArticleScientific reports2020
Inhibition of cyclooxygenase-1 by nonsteroidal anti-inflammatory drugs demethylates MeR2 enhancer and promotes Mbnl1 transcription in myogenic cells.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 18 citations in OpenAlex.
- Direct Oral Anticoagulants, COX-2-Selective NSAIDs, and Gastrointestinal Bleeding in Atrial Fibrillation.JAMA network open · 2026Article
- MBNL proteins in health, disease, and therapeutic applications.Nucleic acids research · 2026Review
- Clinicopathological-genetic features of neutral lipid storage disease with myopathy from a Chinese neuromuscular center.Orphanet journal of rare diseases · 2025Article
- A drug repurposing screen reveals dopamine signaling as a critical pathway underlying potential therapeutics for the rare disease DPAGT1-CDG.PLoS genetics · 2024Article
- Clinicopathological-genetic features of congenital myasthenic syndrome from a Chinese neuromuscular centre.Journal of cellular and molecular medicine · 2022Article
- Partners in crime: Proteins implicated in RNA repeat expansion diseases.Wiley interdisciplinary reviews. RNA · 2022Review
- Overview of the Complex Relationship between Epigenetics Markers, CTG Repeat Instability and Symptoms in Myotonic Dystrophy Type 1.International journal of molecular sciences · 2022Review
- Article
- Findings of limb-girdle muscular dystrophy R7 telethonin-related patients from a Chinese neuromuscular center.Neurogenetics · 2022Article
- Disrupting the Molecular Pathway in Myotonic Dystrophy.International journal of molecular sciences · 2021Review
- Preclinical characterization of antagomiR-218 as a potential treatment for myotonic dystrophy.Molecular therapy. Nucleic acids · 2021Article
- Expanding the clinicopathological-genetic spectrum of GNE myopathy by a Chinese neuromuscular centre.Journal of cellular and molecular medicine · 2021Article
- Identification of a Prenyl Chalcone as a Competitive Lipoxygenase Inhibitor: Screening, Biochemical Evaluation and Molecular Modeling Studies.Molecules (Basel, Switzerland) · 2021Article
- Repositive RT-PCR test in discharged COVID-19 patients during medical isolation observation.International journal of medical sciences · 2021Article
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Authors and funding
10 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Muscleblind-like 1 (MBNL1) is a ubiquitously expressed RNA-binding protein, which is highly expressed in skeletal muscle. Abnormally expanded CUG-repeats in the DMPK gene cause myotonic dystrophy type 1 (DM1) by sequestration of MBNL1 to nuclear RNA foci and by upregulation of another RNA-binding protein, CUG-binding protein 1 (CUGBP1). We previously reported that a nonsteroidal anti-inflammatory drug (NSAID), phenylbutazone, upregulates MBNL1 expression in DM1 mouse model by demethylation of MeR2, an enhancer element in Mbnl1 intron 1. NSAIDs inhibit cyclooxygenase (COX), which is comprised of COX-1 and COX-2 isoforms. In this study, we screened 29 NSAIDs in C2C12 myoblasts, and found that 13 NSAIDs enhanced Mbnl1 expression, where COX-1-selective NSAIDs upregulated Mbnl1 more than COX-2-selective NSAIDs. Consistently, knockdown of COX-1, but not of COX-2, upregulated MBNL1 expression in C2C12 myoblasts and myotubes, as well as in myotubes differentiated from DM1 patient-derived induced pluripotent stem cells (iPSCs). Luciferase assay showed that COX-1-knockdown augmented the MeR2 enhancer activity. Furthermore, bisulfite sequencing analysis demonstrated that COX-1-knockdown suppressed methylation of MeR2. These results suggest that COX-1 inhibition upregulates Mbnl1 transcription through demethylation of the MeR2 enhancer. Taken together, our study provides new insights into the transcriptional regulation of Mbnl1 by the COX-1-mediated pathway.
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