ArticleOncogene2014
JARID2 is a direct target of the PAX3-FOXO1 fusion protein and inhibits myogenic differentiation of rhabdomyosarcoma cells.
Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 105 citations in OpenAlex.
- PAX3: A Driver of Normal Development and Disease.Biomolecules · 2026Review
- Article
- Fusion oncogenes in rhabdomyosarcoma: model systems, mechanisms of tumorigenesis, and therapeutic implications.Frontiers in oncology · 2025Review
- Patient-derived tumor organoid and fibroblast assembloid models for interrogation of the tumor microenvironment in esophageal adenocarcinoma.Cell reports methods · 2024Article
- Article
- Mechanisms Underlying the Rarity of Skeletal Muscle Cancers.International journal of molecular sciences · 2024Review
- Exosome-Mediated Paracrine Signaling Unveils miR-1246 as a Driver of Aggressiveness in Fusion-Negative Rhabdomyosarcoma.Cancers · 2024Article
- Pharmacological EZH2 inhibition combined with retinoic acid treatment promotes differentiation and apoptosis in rhabdomyosarcoma cells.Clinical epigenetics · 2023Article
- Small Molecule Inhibitors as Therapeutic Agents Targeting Oncogenic Fusion Proteins: Current Status and Clinical.Molecules (Basel, Switzerland) · 2023Review
- Genomic and Epigenetic Changes Drive Aberrant Skeletal Muscle Differentiation in Rhabdomyosarcoma.Cancers · 2023Review
- Polycomb Repressive Complex 2 in Oncology.Cancer treatment and research · 2023Article
- Critical Roles of Polycomb Repressive Complexes in Transcription and Cancer.International journal of molecular sciences · 2022Review
- Mechanisms of Polycomb group protein function in cancer.Cell research · 2022Review
- Distinct binding pattern of EZH2 and JARID2 on RNAs and DNAs in hepatocellular carcinoma development.Frontiers in oncology · 2022Article
- Article
- Long noncoding RNA matrilineal expression gene 3 inhibits hepatocellular carcinoma progression by targeting microRNA-5195-3p and regulating the expression of forkhead box O1.Bioengineered · 2021Article
- BAF complexes drive proliferation and block myogenic differentiation in fusion-positive rhabdomyosarcoma.Nature communications · 2021Article
- Reduced B7-H3 expression by PAX3-FOXO1 knockdown inhibits cellular motility and promotes myogenic differentiation in alveolar rhabdomyosarcoma.Scientific reports · 2021Article
- Article
- Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Rhabdomyosarcomas (RMS) are the most frequent soft-tissue sarcoma in children and characteristically show features of developing skeletal muscle. The alveolar subtype is frequently associated with a PAX3-FOXO1 fusion protein that is known to contribute to the undifferentiated myogenic phenotype of RMS cells. Histone methylation of lysine residues controls developmental processes in both normal and malignant cell contexts. Here we show that JARID2, which encodes a protein known to recruit various complexes with histone-methylating activity to their target genes, is significantly overexpressed in RMS with PAX3-FOXO1 compared with the fusion gene-negative RMS (t-test; P < 0.0001). Multivariate analyses showed that higher JARID2 levels are also associated with metastases at diagnosis, independent of fusion gene status and RMS subtype (n = 120; P = 0.039). JARID2 levels were altered by silencing or overexpressing PAX3-FOXO1 in RMS cell lines with and without the fusion gene, respectively. Consistent with this, we demonstrated that JARID2 is a direct transcriptional target of the PAX3-FOXO1 fusion protein. Silencing JARID2 resulted in reduced cell proliferation coupled with myogenic differentiation, including increased expression of Myogenin (MYOG) and Myosin Light Chain (MYL1) in RMS cell lines representative of both the alveolar and embryonal subtypes. Induced myogenic differentiation was associated with a decrease in JARID2 levels and this phenotype could be rescued by overexpressing JARID2. Furthermore, we that showed JARID2 binds to and alters the methylation status of histone H3 lysine 27 in the promoter regions of MYOG and MYL1 and that the interaction of JARID2 at these promoters is dependent on EED, a core component of the polycomb repressive complex 2 (PRC2). Therefore, JARID2 is a downstream effector of PAX3-FOXO1 that maintains an undifferentiated myogenic phenotype that is characteristic of RMS. JARID2 and other components of PRC2 may represent novel therapeutic targets for treating RMS patients.
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