Verdier Elodie, Gaspar Nathalie, Marques Da Costa Maria Eugenia, Marchais Antonin
UMR 1015 Tumour Immunology and anti-cancer immunotherapy Unit, Gustave Roussy Cancer Campus, Villejuif 94800, France.
Department of Oncology for Child and Adolescent, Gustave Roussy Cancer Campus, Université Paris-Saclay, Villejuif 94805, France.
Oncotarget. 2025 Feb 12;16:51-62. doi: 10.18632/oncotarget.28688.
Epigenetic modifications, which reversibly regulate gene expression without altering the DNA sequence, are increasingly described in the literature as essential elements in the processes leading to cancer development. SETDB1 regulates histone 3 (H3) K9 di- and trimethylation, promoting heterochromatin formation, and plays a key role in gene silencing. Epigenetic deregulation of expression appears to be involved in different cancers types, particularly in aggressive, relapsing or treatment-resistant subtypes. Despite advances in research, the full range of mechanisms through which this protein acts remains unclear; however, it is evident that SETDB1 has a pivotal role, particularly in the mesenchymal stem cells differentiation, tumor evasion and treatment resistance. Its role in genetically complex sarcomas, such as osteosarcoma, has not been fully explored, although recent Omics analyses suggest its presence and amplification in osteosarcoma. Given its involvement in osteoblastogenesis and adipogenesis, we discuss the potential of SETDB1 as a key target for new therapeutic strategies in osteosarcoma.
表观遗传修饰可在不改变DNA序列的情况下可逆地调节基因表达，在导致癌症发展的过程中，越来越多的文献将其描述为关键因素。SETDB1调节组蛋白3（H3）的K9二甲基化和三甲基化，促进异染色质形成，并在基因沉默中起关键作用。SETDB1表达的表观遗传失调似乎与不同类型的癌症有关，尤其是侵袭性、复发性或难治性亚型。尽管研究取得了进展，但该蛋白发挥作用的全部机制仍不清楚；然而，很明显SETDB1具有关键作用，特别是在间充质干细胞分化、肿瘤逃逸和治疗耐药性方面。尽管最近的组学分析表明其在骨肉瘤中存在并扩增，但其在骨肉瘤等基因复杂的肉瘤中的作用尚未得到充分探索。鉴于其参与成骨细胞生成和脂肪生成，我们讨论了SETDB1作为骨肉瘤新治疗策略关键靶点的潜力。
