ArticleThe Journal of biological chemistry2015
Alternative splicing of MEF2C pre-mRNA controls its activity in normal myogenesis and promotes tumorigenicity in rhabdomyosarcoma cells.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 76 citations in OpenAlex.
- The Diverse Roles of the MEF2 Transcription Factor Family in Tumor Progression and Emerging Therapeutic Opportunities.Biomedicines · 2026Review
- From splicing to disease: the crucial role of serine/arginine protein kinases in cellular regulation.Molecular biology reports · 2026Review
- Novel insights into the molecular mechanisms of LGMDD2: role of TNPO3 in experimental cell and zebrafish models.Cellular and molecular life sciences : CMLS · 2025Article
- Article
- Molecular Targets in Alveolar Rhabdomyosarcoma: A Narrative Review of Progress and Pitfalls.International journal of molecular sciences · 2025Review
- The universal role of adaptive transcription in health and disease.The FEBS journal · 2025Review
- The Development of Selective Chemical Probes for Serine Arginine Protein Kinase 3.Chemical biology & drug design · 2025Article
- Construction of a prognostic model for gastric cancer based on immune infiltration and microenvironment, and exploration of MEF2C gene function.BMC medical genomics · 2025Article
- The Spatial-Temporal Alternative Splicing Profile Reveals the Functional Diversity of FXR1 Isoforms in Myogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Pathomechanisms of Monoallelic variants in TTN causing skeletal muscle disease.Human molecular genetics · 2024Article
- Mining alternative splicing patterns in scRNA-seq data using scASfind.Genome biology · 2024Article
- The RNA-binding protein QKI governs a muscle-specific alternative splicing program that shapes the contractile function of cardiomyocytes.Cardiovascular research · 2023Article
- Electrospun Poly(L-lactide-co-ε-caprolactone) Scaffold Potentiates C2C12 Myoblast Bioactivity and Acts as a Stimulus for Cell Commitment in Skeletal Muscle Myogenesis.Bioengineering (Basel, Switzerland) · 2023Article
- Aging, adaptation and maladaptation.Frontiers in aging · 2023Article
- Novel Compound Heterozygous Splice-Site Variants in TPM3 Revealed by RNA Sequencing in a Patient with an Unusual Form of Nemaline Myopathy: A Case Report.Journal of neuromuscular diseases · 2023Article
- Identification and functional prediction of long non-coding RNAs related to skeletal muscle development in Duroc pigs.Animal bioscience · 2022Article
- Quercetin induces pannexin 1 expression via an alternative transcript with a translationally active 5' leader in rhabdomyosarcoma.Oncogenesis · 2022Article
- Therapeutic Targeting of Alternative Splicing: A New Frontier in Cancer Treatment.Frontiers in oncology · 2022Review
- Article
- Large-scale transcriptome sequencing in broiler chickens to identify candidate genes for breast muscle weight and intramuscular fat content.Genetics, selection, evolution : GSE · 2021Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Many cellular disruptions contribute to the progression of this pediatric cancer, including aberrant alternative splicing. The MEF2 family of transcription factors regulates many developmental programs, including myogenesis. MEF2 gene transcripts are subject to alternate splicing to generate protein isoforms with divergent functions. We found that MEF2Cα1 was the ubiquitously expressed isoform that exhibited no myogenic activity and that MEF2Cα2, the muscle-specific MEF2C isoform, was required for efficient differentiation. We showed that exon α in MEF2C was aberrantly alternatively spliced in RMS cells, with the ratio of α2/α1 highly down-regulated in RMS cells compared with normal myoblasts. Compared with MEF2Cα2, MEF2Cα1 interacted more strongly with and recruited HDAC5 to myogenic gene promoters to repress muscle-specific genes. Overexpression of the MEF2Cα2 isoform in RMS cells increased myogenic activity and promoted differentiation in RMS cells. We also identified a serine protein kinase, SRPK3, that was down-regulated in RMS cells and found that expression of SRPK3 promoted the splicing of the MEF2Cα2 isoform and induced differentiation. Restoration of either MEF2Cα2 or SPRK3 inhibited both proliferation and anchorage-independent growth of RMS cells. Together, our findings indicate that the alternative splicing of MEF2C plays an important role in normal myogenesis and RMS development. An improved understanding of alternative splicing events in RMS cells will potentially reveal novel therapeutic targets for RMS treatment.
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