Department of Orthopedics, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China.
Department of Radiology, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, China.
Mol Carcinog. 2024 Aug;63(8):1599-1610. doi: 10.1002/mc.23748. Epub 2024 May 31.
Osteosarcoma (OS) is a common primary malignant bone tumor, and it is necessary to further investigate the molecular mechanism of OS progression. The expression of kinetochore associated protein 1 (KNTC1) and minichromosome maintenance 2 (MCM2) was detected by immunohistochemistry, quantitative PCR (qPCR) and Western blot. Gene knockdown or overexpression cell models were constructed and the proliferation, apoptosis, cell cycle and migration were detected in vitro, besides, xenograft models were established to explore the effects of KNTC1 downregulation in vivo. Public databased and bioinformatics analysis were performed to screen the downstream molecules and determine the expression of MCM2 in cancers. KNTC1 was overexpressed in OS tissues and positively correlated with overall survival of OS patients. KNTC1 knockdown inhibited the proliferation and migration, and arrested G2 phase, and induced apoptosis. Besides, KNTC1 downregulation restricted the xenograft tumor formation. MCM2, one of the coexpressed genes, was highly expressed in sarcoma and downregulated after KNTC1 knockdown. MCM2 overexpression heightened the proliferation and migration ability of OS cells, which was reversed the inhibiting effects of KNTC1 knockdown. KNTC1 was overexpressed in OS and promoted the progression of OS by upregulating MCM2.
骨肉瘤（OS）是一种常见的原发性恶性骨肿瘤，有必要进一步研究 OS 进展的分子机制。通过免疫组织化学、定量 PCR（qPCR）和 Western blot 检测着丝粒相关蛋白 1（KNTC1）和微小染色体维持蛋白 2（MCM2）的表达。构建基因敲低或过表达细胞模型，检测体外增殖、凋亡、细胞周期和迁移，此外，还建立了异种移植模型以体内研究 KNTC1 下调的作用。进行了公共数据库和生物信息学分析以筛选下游分子并确定 MCM2 在癌症中的表达。KNTC1 在 OS 组织中过表达，并与 OS 患者的总生存率呈正相关。KNTC1 敲低抑制增殖和迁移，使 G2 期停滞，并诱导凋亡。此外，KNTC1 下调限制了异种移植肿瘤的形成。MCM2 是共表达基因之一，在肉瘤中高表达，并且在 KNTC1 敲低后表达下调。MCM2 过表达增强了 OS 细胞的增殖和迁移能力，这逆转了 KNTC1 敲低的抑制作用。KNTC1 在 OS 中过表达，通过上调 MCM2 促进 OS 的进展。
