骨肉瘤（OS）是最常见的原发性恶性骨肿瘤，其异质性是常见抗肿瘤治疗的主要挑战。已知炎症细胞因子对于 OS 进展是必需的。因此，为了优化治疗，重要的是通过识别产生 OS 的机制并研究支持未分化状态的炎症途径来发现可靠的生物标志物。在这项工作中，我们强调了三种不同 OS 细胞系肿瘤进展中 IL-1β 和 TNFα 表观遗传活性的差异，以及 TET-1 酶抑制的敏感性。通过研究 IL-6 启动子的 DNA 甲基化并确定其表达，我们发现 TET 酶抑制会影响 OS 细胞系中炎症细胞因子诱导的增殖。此外，Bobcat 339 治疗可阻断 IL-1β 对 IL-6 启动子的表观遗传作用，而仅部分抑制 TNFα 的表观遗传作用，并抑制 IL-1β 依赖性上皮间质转化 (EMT) 过程，但仅部分抑制 TNFα 的表观遗传作用。总之，这项工作强调 IL-1β 和 TNFα 对 OS 细胞系中 DNA 去甲基化有不同的影响，使 DNA 甲基化成为潜在的疾病生物标志物。具体来说，在 IL-1β 治疗中，TET-1 抑制完全阻止肿瘤进展，而在 TNFα 作用中，它仅部分有效。鉴于这两种炎症途径可以作为治疗这些肿瘤的治疗靶点，了解它们独特的表观遗传行为可有助于制定针对这种疾病的精确和特异性的治疗策略。© 2024。作者。

Osteosarcoma (OS) is the most frequent primary malignant bone tumour, whose heterogeneity represents a major challenge for common antitumour therapies. Inflammatory cytokines are known to be necessary for OS progression. Therefore, to optimise therapy, it is important to discover reliable biomarkers by identifying the mechanism generating OS and investigating the inflammatory pathways that support the undifferentiated state. In this work, we highlight the differences of epigenetic activities of IL-1β and TNFα, and the susceptibility of TET-1 enzymatic inhibition, in tumour progression of three different OS cell lines. Investigating DNA methylation of IL-6 promoter and determining its expression, we found that TET enzymatic inhibition influences proliferation induced by inflammatory cytokines in OS cell lines. Moreover, Bobcat 339 treatment blocks IL-1β epigenetic action on IL-6 promoter, while only partially those of TNFα as well as inhibits IL-1β-dependent epithelial-mesenchymal transition (EMT) process, but only partially those of TNFα. In conclusion, this work highlights that IL-1β and TNFα have different effects on DNA demethylation in OS cell lines, making DNA methylation a potential biomarker of disease. Specifically, in IL-1β treatment, TET-1 inhibition completely blocks tumour progression, while in TNFα actions, it is only partially effective. Given that these two inflammatory pathways can be therapeutic targets for treating these tumours, knowledge of their distinct epigenetic behaviours can be useful for developing precise and specific therapeutic strategies for this disease.© 2024. The Author(s).