Shi Ce, Chen Lei, Huang Kui, Yang Guanghui, Shi Tingting, Li Jinshuang, Zheng Hongbing
Department of Orthopedics, The Affiliated Suqian Hospital of Xuzhou Medical University, Suqian, 223800, China.
Department of Oncology, The Affiliated Suqian Hospital of Xuzhou Medical University, Suqian, 223800, China.
Prog Biophys Mol Biol. 2024 Dec;194:34-42. doi: 10.1016/j.pbiomolbio.2024.10.003. Epub 2024 Oct 25.
Osteosarcoma (OS) represents the primary form of bone cancer observed in paediatric and adolescent populations. Nearly 10%-15% of patients have metastases at diagnosis, and the 5-year survival rate was less than 20%. Although numerous investigators have offered significant efforts, the survival rates for patients with OS have remained almost unchanged over the past three decades. The most pervasive and abundant modification of internal transcripts in eukaryotic messenger RNAs (mRNAs) is N6-methyladenosine (m6A), and it is regulated by m6A methylation regulators. A number of recent studies have demonstrated that m6A modifications can regulate the biological activities of tumour cells and are intimately linked with cancer development, prognosis, drug resistance, and therapy. N6-methyladenosine modification of Non-coding RNA (ncRNA) has likewise shown a broad potential in gene regulation and tumor biology. Epigenetic changes induced by mRNAs and ncRNAs methylation are important for a better understanding of OS development and targeted drug development. Therefore, this paper summarises the biological functions of m6A-modified regulators in osteosarcoma and the role of mutual regulation between m6A and ncRNAs in osteosarcoma. Furthermore, the potential clinical applications of m6A modifications in OS are presented for consideration. It provides new directions for the future research and clinical treatment strategies of osteosarcoma.
骨肉瘤(OS)是儿童和青少年中观察到的原发性骨癌形式。近10%-15%的患者在诊断时已有转移,5年生存率低于20%。尽管众多研究人员付出了巨大努力,但在过去三十年中,骨肉瘤患者的生存率几乎没有变化。真核生物信使核糖核酸(mRNA)中最普遍且丰富的内部转录本修饰是N6-甲基腺苷(m6A),它受m6A甲基化调节因子调控。最近的一些研究表明,m6A修饰可调节肿瘤细胞的生物学活性,并与癌症的发生、预后、耐药性及治疗密切相关。非编码核糖核酸(ncRNA)的N6-甲基腺苷修饰在基因调控和肿瘤生物学方面同样显示出广泛潜力。mRNA和ncRNA甲基化诱导的表观遗传变化对于更好地理解骨肉瘤的发生发展及靶向药物研发具有重要意义。因此,本文总结了m6A修饰的调节因子在骨肉瘤中的生物学功能以及m6A与ncRNAs在骨肉瘤中的相互调控作用。此外,还探讨了m6A修饰在骨肉瘤中的潜在临床应用。它为骨肉瘤未来的研究和临床治疗策略提供了新方向。