The Role and Mechanism of m6A Methylation Modification in Osteosarcoma

骨肉瘤(osteosarcoma, OS)是儿童和青少年最常见的原发性骨恶性肿瘤，具有高度侵袭性和转移性，且预后不良，患者的5年生存率较低。N6-甲基腺苷(N6-methyladenosine, m6A)是真核细胞mRNA修饰中最常见的一种，在众多的生物学活动中都起到重要作用。最近研究发现，m6A甲基化修饰在RNA甲基化中扮演了关键角色，通过对“writer”，“eraser”和“reader”等分子的动态调节，参与mRNA的剪接、去核翻译、降解和稳定等生物学过程，对多种疾病产生重要影响，包括癌症。RNA的m6A甲基化与骨肉瘤密切相关，但机制尚未明确。本文就m6A修饰及其相关酶在骨肉瘤生物学功能中的调控机制，以及其在骨肉瘤发病机制、预后中的作用研究进展作一综述，可能为骨肉瘤的治疗提供新的思路与理论依据。Osteosarcoma (OS), the most prevalent primary malignant bone tumor in children and adolescents, exhibits high invasiveness, metastatic potential, and poor prognosis, with notably low 5-year survival rates. N6-methyladenosine (m6A), the predominant post-transcriptional modification in eukaryotic mRNA, plays crucial regulatory roles in diverse biological processes. Emerging evidence reveals that m6A methylation critically modulates RNA metabolism through dynamic coordination of “writer”, “eraser”, and “reader”, thereby governing mRNA splicing, nucleocytoplasmic transport, translation efficiency, degradation, and stability. This epigenetic mechanism significantly impacts various pathological processes, including carcinogenesis. Although RNA m6A methylation demonstrates close associations with osteosarcoma progression, its underlying mechanisms remain incompletely elucidated. This review systematically examines current advances in understanding the regulatory mechanisms of m6A modifications and associated enzymes in osteosarcoma biology, with emphasis on their pathophysiological roles in tumorigenesis, and prognostic evaluation. The synthesis of these findings may provide novel therapeutic strategies and theoretical foundations for improving clinical management of osteosarcoma.