Identifacation Kinesin family member 2A (KIF2A) as a promising therapeutic target for osteosarcoma
Identifacation Kinesin family member 2A (KIF2A) as a promising therapeutic target for osteosarcoma
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鉴定驱动蛋白家族成员 2A (KIF2A) 作为骨肉瘤有前景的治疗靶点
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通讯作者：
Jing Ren
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作者：
Zhe-Xiang Wang;Shao-Chun Ren;Jing Ren
背景：骨肉瘤是一种常见的人类骨恶性肿瘤，对抗该疾病仍需要更多的治疗靶点。近年来，KIF2A 参与癌症进展已被广泛揭示，但其对骨肉瘤发展的潜在影响仍不清楚。本研究旨在评估人骨肉瘤组织中KIF2A的表达水平并探讨其在骨肉瘤发展中的潜在作用。方法：采用免疫组织化学（IHC）检测方法评估总共 74 例骨肉瘤组织和癌旁非肿瘤组织样本中 KIF2A 的表达水平。根据肿瘤组织中的染色强度将患者分为高表达组和低表达组。探讨和分析KIF2A表达与临床病理特征之间可能的联系，并分别通过集落形成实验、MTT实验、伤口闭合实验和Transwell实验检测KIF2A对骨肉瘤细胞增殖、迁移和侵袭的影响。通过动物模型检测KIF2A对肿瘤生长和转移的影响。结果：KIF2A在人骨肉瘤组织中高表达。同时，KIF2A与骨肉瘤患者的肿瘤大小（P=0.001*）和临床分期（P=0.014*）明显相关。我们的结果还表明，KIF2A 的消融可显着阻断体外骨肉瘤细胞的增殖、迁移和侵袭能力，并阻断小鼠体内的肿瘤生长和转移。结论：我们研究了 KIF2A 在骨肉瘤的发生和转移中的参与，因此认为 KIF2A 是骨肉瘤治疗的一个有前途的治疗靶点。
Background: Osteosarcoma is known as a type of common human bone malignancy, and more therapeutic targets are still requirement to combat this disease. In recent years, the involvement of KIF2A in cancer progression has been widely revealed, however, its potential effect on osteosarcoma development remains unknown. This study is to assess KIF2A expression levels in human osteosarcoma tissues and explore its potential role in osteosarcoma development. Methods: Immunohistochemical (IHC) assays were conducted to evaluate the expression levels of KIF2A in a total of 74 samples of osteosarcoma tissues and adjacent non-tumor tissues. According to the staining intensity in tumor tissues, patients were divided into highly expressed and low expression KIF2A groups. The possible links between KIF2A expression and clinical pathological features were explored and analyzed, and the effects of KIF2A on osteosarcoma cell proliferation, migration, and invasion were detected through colony formation assay, MTT assay, wound closure assay and transwell assay, respectively. The effects of KIF2A on tumor growth and metastasis were detected by the use of animal modes. Results: KIF2A was highly expressed in human osteosarcoma tissues. Meanwhile, KIF2A was obviously correlated to the tumor size (P=0.001*) and clinical stage (P=0.014*) of osteosarcoma patients. Our results also revealed that ablation of KIF2A dramatically blocked the proliferation, migration, and invasion capacity of osteosarcoma cells in vitro and blocked tumor growth and metastasis in mice. Conclusions: We investigated the involvement of KIF2A in the development and metastasis of osteosarcoma, and therefore thought KIF2A as a promising therapeutic target for osteosarcoma treatment.