Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Department of Musculoskeletal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
Chemotherapy. 2019;64(4):187-196. doi: 10.1159/000505014. Epub 2020 Feb 19.
Kinesin family (KIF) members have vital roles in mitosis, meiosis, and transport of macromolecules in eukaryotic cells. In this study, we aimed to investigate the role of KIF15 in osteosarcoma. Immunohistochemical staining was performed to determine expression levels of KIF15 in osteosarcoma tissues and adjacent normal tissues. Tissue microarray analysis showed a correlation between the expression of KIF15 and pathological features of patients. Subsequently, lentivirus was used to inhibit the expression of KIF15 in osteosarcoma cells. An MTT assay was performed to examine cell proliferation. Transwell and wound healing assays were used to estimate the invasion and migration of osteosarcoma cells, respectively. Flow cytometric analysis was employed to define the apoptosis of osteosarcoma cells. Our results showed that KIF15 expression was significantly upregulated in osteosarcoma tissues compared with adjacent normal tissues. The Mann-Whitney U test and Spearman correlation analysis showed that the expression levels of KIF15 in osteosarcoma tissues were positively correlated with tumor infiltrate, a pathological characteristic of patients. The expression of KIF15 was successfully suppressed by shKIF15, and the knockdown efficiency reached 80 and 69% in MNNG/HOS and U2OS cells, respectively. Subsequently, knockdown of KIF15 significantly inhibited the capacity of cell proliferation, colony formation, invasion, and migration, but enhanced G2 phase arrest and partially enhanced cell apoptosis. This study preliminarily showed KIF15 to be a critical regulatory molecule involved in osteosarcoma cell proliferation. Consequently, KIF15 can be a potential diagnostic and therapeutic target for osteosarcoma.
驱动蛋白家族（KIF）成员在真核细胞的有丝分裂、减数分裂和大分子运输中发挥着重要作用。在这项研究中，我们旨在研究 KIF15 在骨肉瘤中的作用。通过免疫组织化学染色来确定 KIF15 在骨肉瘤组织和相邻正常组织中的表达水平。组织微阵列分析显示 KIF15 的表达与患者的病理特征之间存在相关性。随后，使用慢病毒抑制骨肉瘤细胞中 KIF15 的表达。通过 MTT assay 检测细胞增殖。Transwell 和划痕愈合assay 分别用于评估骨肉瘤细胞的侵袭和迁移。流式细胞术分析用于定义骨肉瘤细胞的凋亡。我们的结果表明，与相邻正常组织相比，骨肉瘤组织中 KIF15 的表达明显上调。Mann-Whitney U 检验和 Spearman 相关分析表明，骨肉瘤组织中 KIF15 的表达水平与肿瘤浸润呈正相关，这是患者的一种病理特征。shKIF15 成功抑制了 KIF15 的表达，在 MNNG/HOS 和 U2OS 细胞中的敲低效率分别达到 80%和 69%。随后，敲低 KIF15 显著抑制了细胞增殖、集落形成、侵袭和迁移的能力，但增强了 G2 期阻滞并部分增强了细胞凋亡。这项研究初步表明 KIF15 是骨肉瘤细胞增殖的关键调节分子。因此，KIF15 可以成为骨肉瘤的潜在诊断和治疗靶点。
