Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Department of Orthopedics, The Second Affiliated Hospital of Anhui Medical University, 678 Furong, Hefei, 230601, China.
Cell Death Dis. 2021 Apr 7;12(4):376. doi: 10.1038/s41419-021-03621-y.
Osteosarcoma is the most common primary malignant tumor of bone derived from osteoblasts, which is a noteworthy threat to the health of children and adolescents. In this study, we found that MCM8 has significantly higher expression level in osteosarcoma tissues in comparison with normal tissues, which was also correlated with more advanced tumor grade and pathological stage. In agreement with the role of MCM proteins as indicators of cell proliferation, knockdown/overexpression of MCM8 inhibited/promoted osteosarcoma cell proliferation in vitro and tumor growth in vivo. Also, MCM8 knockdown/overexpression was also significantly associated with the promotion/inhibition of cell apoptosis and suppression/promotion of cell migration. More importantly, mechanistic study identified CTGF as a potential downstream target of MCM8, silencing of which could enhance the regulatory effects of MCM8 knockdown and alleviate the effects of MCM8 overexpression on osteosarcoma development. In summary, MCM8/CTGF axis was revealed as critical participant in the development and progression of osteosarcoma and MCM8 may be a promising therapeutic target for osteosarcoma treatment.
骨肉瘤是一种源自成骨细胞的最常见原发性骨恶性肿瘤，是儿童和青少年健康的重大威胁。在本研究中，我们发现 MCM8 在骨肉瘤组织中的表达水平明显高于正常组织，并且与更高级别的肿瘤分级和病理分期相关。与 MCM 蛋白作为细胞增殖指标的作用一致，MCM8 的敲低/过表达抑制/促进了体外骨肉瘤细胞的增殖和体内肿瘤的生长。此外，MCM8 的敲低/过表达与促进/抑制细胞凋亡以及抑制/促进细胞迁移显著相关。更重要的是，机制研究确定 CTGF 是 MCM8 的潜在下游靶标，沉默 CTGF 可以增强 MCM8 敲低的调节作用，并减轻 MCM8 过表达对骨肉瘤发展的影响。总之，MCM8/CTGF 轴被揭示为骨肉瘤发生和发展的关键参与者，MCM8 可能是骨肉瘤治疗有前途的治疗靶点。
