Magar Anuja Gajanan, Morya Vivek Kumar, Noh Kyu-Cheol
School of Medicine, Hallym University, Chuncheon-si 24252, Republic of Korea.
Hallym University Sacred Heart Hospital, Anyang-si 14068, Republic of Korea.
Int J Mol Sci. 2025 Aug 7;26(15):7642. doi: 10.3390/ijms26157642.
Runt-related transcription factor-2 (RUNX2) is an integral player in osteogenesis and is highly expressed in osteosarcoma. Emerging evidence suggests that aberrant RUNX2 expression is a key factor in osteosarcoma oncogenesis. Patients with advanced stages of osteosarcoma overexpressing RUNX2 are more likely to have high tumour grades, metastasis, and lower overall or progression-free survival rates. Thus, RUNX2 is considered a potential candidate for targeted therapy of osteosarcoma. Hypoxia-inducible factor-1α (HIF-1α) is a key transcription factor involved in the regulation of cellular reprogramming in response to hypoxia. Overexpression of HIF-1α decreases overall survival, disease-free survival, and chemotherapy response and promotes tumour stage and metastasis. Hence, our review focused on highlighting the intricate network between RUNX2 and HIF-1α, which support each other or may work synergistically to develop resistance to therapy and osteosarcoma progression. An in-depth understanding of these two important tumour progression markers is required. Therefore, this review focuses on the role of RUNX2 and HIF-1α in the alteration of the tumour microenvironment, which further promotes angiogenesis, metastasis, and resistance to therapy in osteosarcoma.
runt相关转录因子2（RUNX2）是成骨过程中的一个重要参与者，在骨肉瘤中高度表达。新出现的证据表明，RUNX2表达异常是骨肉瘤发生的关键因素。过表达RUNX2的晚期骨肉瘤患者更有可能具有高肿瘤分级、转移，以及更低的总生存率或无进展生存率。因此，RUNX2被认为是骨肉瘤靶向治疗的一个潜在候选靶点。缺氧诱导因子-1α（HIF-1α）是一种关键转录因子，参与调节细胞对缺氧的重编程反应。HIF-1α的过表达会降低总生存率、无病生存率和化疗反应，并促进肿瘤分期和转移。因此，我们的综述重点强调了RUNX2和HIF-1α之间复杂的网络，它们相互支持或可能协同作用，导致对治疗产生耐药性并促进骨肉瘤进展。需要深入了解这两个重要的肿瘤进展标志物。因此，本综述重点关注RUNX2和HIF-1α在肿瘤微环境改变中的作用，这进一步促进了骨肉瘤中的血管生成、转移和对治疗的耐药性。
