Liu Ya-Yun, Sun Wu, Liu Lin, Cheng Jin-Hui, Li Jing-Tang, Huang Zu-Tai, Ouyang Min
Department of Orthopaedics, Jiangxi Provincial People's Hospital, the First Affiliated Hospital of Nanchang Medical College, Nanchang, People's Republic of China.
Discipline of Chinese and Western Integrative Medicine, Jiangxi University of Chinese Medicine, Nanchang, People's Republic of China.
Cancer Med. 2025 May;14(9):e70915. doi: 10.1002/cam4.70915.
Although kinesin family member 2C (KIF2C) is implicated in various cancers, its role in osteosarcoma (OS) and the associated inflammatory microenvironment remains unclear.
Publicly available datasets were analyzed to determine KIF2C expression, diagnostic value, and prognostic relevance in OS. In vitro (proliferation, colony formation, apoptosis, migration, invasion) and in vivo assays assessed its biological functions. KEGG enrichment and GSVA explored underlying pathways. ssGSEA, ESTIMATE algorithms, and single-cell sequencing evaluated the immune context, and molecular docking and molecular dynamics identified potential inhibitory compounds.
KIF2C was significantly overexpressed in OS, effectively distinguishing OS from normal tissues. Elevated KIF2C levels correlated with poor survival outcomes. Silencing KIF2C suppressed OS cell proliferation, migration, invasion, and in vivo tumor growth, while promoting apoptosis; conversely, overexpression of KIF2C had the opposite effect. Mechanistically, co-immunoprecipitation results indicated that KIF2C can bind to β-catenin to regulate the Wnt/β-catenin pathway. Furthermore, high KIF2C expression was associated with an immunosuppressive tumor microenvironment characterized by immune exhaustion. Molecular docking and molecular dynamics suggested butein as a candidate small-molecule inhibitor targeting KIF2C-related oncogenic mechanisms.
KIF2C drives OS progression by enhancing Wnt/β-catenin signaling and fostering an immunosuppressive microenvironment. Targeting KIF2C may offer new therapeutic approaches in managing OS.
尽管驱动蛋白家族成员2C（KIF2C）与多种癌症有关，但其在骨肉瘤（OS）及相关炎症微环境中的作用仍不清楚。
分析公开可用的数据集，以确定KIF2C在骨肉瘤中的表达、诊断价值和预后相关性。体外实验（增殖、集落形成、凋亡、迁移、侵袭）和体内实验评估其生物学功能。KEGG富集分析和基因集变异分析（GSVA）探索潜在途径。单样本基因集富集分析（ssGSEA）、肿瘤免疫估计（ESTIMATE）算法和单细胞测序评估免疫背景，分子对接和分子动力学确定潜在的抑制化合物。
KIF2C在骨肉瘤中显著过表达，能有效区分骨肉瘤与正常组织。KIF2C水平升高与不良生存结果相关。沉默KIF2C可抑制骨肉瘤细胞增殖、迁移、侵袭及体内肿瘤生长，同时促进细胞凋亡；相反，KIF2C过表达则产生相反效果。机制上，免疫共沉淀结果表明KIF2C可与β-连环蛋白结合以调节Wnt/β-连环蛋白信号通路。此外，高KIF2C表达与以免疫耗竭为特征的免疫抑制肿瘤微环境相关。分子对接和分子动力学表明，白杨素是一种靶向KIF2C相关致癌机制的候选小分子抑制剂。
KIF2C通过增强Wnt/β-连环蛋白信号传导和促进免疫抑制微环境来驱动骨肉瘤进展。靶向KIF2C可能为骨肉瘤的治疗提供新方法。
