Osteosarcoma (OS) is the most commonly diagnosed primary malignant bone tumor in children and adolescents. Despite significant advancements in therapeutic strategies against OS over the past few decades, the prognosis for this disease remains poor, largely due to its high invasiveness and challenges associated with its treatment. N6-methyladenosine (m6A) modification is one of the most abundant epigenetic modifications of RNAs, and many studies have highlighted its crucial role in OS. This article provides a comprehensive summary and introduction to m6A regulators, including methyltransferases, demethylases, and binding proteins. The article emphasizes how regulated m6A modifications can either promote or inhibit OS. It also delves into the mechanisms by which m6A-modified messenger RNAs (mRNAs) and noncoding RNAs (ncRNAs) participate in signaling pathways such as the Wnt/β-catenin, PI3K/AKT, and STAT3 pathways, and discusses these mechanisms in detail. Given the abnormal expression of m6A regulators in OS, the article also explores their potential applications as biomarkers or therapeutic targets in clinical settings. It is anticipated that this review will provide new insights into the diagnosis and treatment of OS.
Keywords: M6A regulator; M6A-modified ncRNA; N6-methyladenosine; Osteosarcoma.
© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.