Epigenetic disruption of adipogenic gene enhancers in dedifferentiated liposarcomas and its therapeutic value
Rattachement africain : jp, us. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Liposarcoma (LPS) is the most common soft-tissue sarcoma in adults, and well-differentiated liposarcoma (WDLPS) and dedifferentiated liposarcoma (DDLPS) are the most frequent subtypes. These LPSs are considered to develop due to disturbances in the adipogenic differentiation of mesenchymal stem cells. However, the molecular mechanisms underlying the disturbances remain unclear. Here, we aimed to identify the mechanism and explore its therapeutic advantages focusing upon their epigenetic alterations, known to be important in differentiation. First, we conducted a genome-wide DNA methylation analysis using 15 LPSs (6 WDLPSs and 9 DDLPSs) and 6 normal adipose tissues. Unsupervised hierarchical cluster analysis using DNA methylation profiles at enhancers classified the samples into the three histological types, whereas analysis using promoters did not. Principal component analysis revealed that normal adipose tissues and WDLPSs were grouped closely, whereas DDLPSs were scattered. Genomic regions hypermethylated in DDLPSs were enriched for enhancers, especially super-enhancers (13.5% of hypermethylated regions and 7.0% of the whole genome), which were located in the genes involved in adipogenesis, such as PPARG2 and its target genes (FABP4 and PLIN1). In addition, marked decreases in PPARG2 and FABP4 expression were confirmed in DDLPSs. Then, treatment of PPARG2-expressing DDLPS cell lines with 5-aza-2’-deoxycytidine, a DNA demethylating agent, and rosiglitazone, a PPARγ agonist, was shown to induce differentiation with enhanced expression of FABP4. These findings indicate that aberrant DNA methylation of adipogenic gene enhancers plays a crucial role in the development of DDLPS and can be a therapeutic target.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Epigenetic disruption of adipogenic gene enhancers in dedifferentiated liposarcomas and its therapeutic value
- Date Crossref
- 30/04/2025
- Éditeur
- Frontiers Media SA
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Gunma University Laboratory of Integrative Metabolic Regulation pays non établi dans la noticeUniversité ou école supérieure
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Hoshi University Department of Epigenomics pays non établi dans la noticeUniversité ou école supérieure
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Keio University Department of Orthopaedic Surgery pays non établi dans la noticeUniversité ou école supérieure
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Maebashi Institute of Technology pays non établi dans la noticeUniversité ou école supérieure
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Quantitative BioSciences pays non établi dans la noticeOrganisation à but non lucratif
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Tokyo National Hospital pays non établi dans la noticeÉtablissement de santé
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National Cancer Center Research Institute Division of Epigenomics pays non établi dans la noticeStructure de recherche
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Faculty of Engineering Department of Life Engineering pays non établi dans la noticeUniversité ou école supérieure
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The University of Tokyo Laboratory of Computational Genomics pays non établi dans la noticeUniversité ou école supérieure
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National Cancer Center Hospital Department of Diagnostic Pathology pays non établi dans la noticeÉtablissement de santé
Laboratory of Integrative Metabolic Regulation — Gunma University, Department of Epigenomics — Hoshi University et Department of Orthopaedic Surgery — Keio University, avec 7 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.