Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, PR China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China; Department of Otolaryngology Head & Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200025, PR China.
Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, PR China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China.
Exp Eye Res. 2019 Aug;185:107598. doi: 10.1016/j.exer.2019.02.014. Epub 2019 Feb 21.
Kinesins are a superfamily of motor proteins and are often dysregulated in many cancers. KIF15, which belongs to the kinesin-12 family, has been shown to function in many different cellular processes, including proliferation, apoptosis, differentiation and development. However, the role of KIF15 in melanoma, remains unknown. In this study, the expression levels of KIF15 in melanoma cells lines and tissues were determined via real-time PCR, immunohistochemical staining and western blot. The effect of KIF15 on tumorigenesis was evaluated by using MTT and colony information. The function of KIF15 on cell survival was detected through flow cytometry assay. Microarray assay and bioinformatics analysis were used to find the potential target of KIF15. We show that KIF15 was significantly upregulated in melanoma cells and tissues. The suppression of KIF15 in tumors significantly reduced tumor growth and increased apoptosis in A375 and OCM1 cells. Findings based on the subcutaneous xenograft model were further consistent with the in vitro results that KIF15 knockdown inhibited melanoma tumor growth in vivo. Microarray assay and bioinformatics indicated that BIRC5, CDK4 and WNT5A were three potential targets of KIF15. Taken together, our results suggest that KIF15 plays a positive role in the tumorigenicity of melanoma and it may serve as a novel diagnostic and therapeutic target for melanoma, especially uveal melanoma.
驱动蛋白是一类马达蛋白超家族，在许多癌症中常失调。属于驱动蛋白-12 家族的 KIF15 已被证明在许多不同的细胞过程中发挥作用，包括增殖、凋亡、分化和发育。然而，KIF15 在黑色素瘤中的作用尚不清楚。在这项研究中，通过实时 PCR、免疫组织化学染色和 Western blot 确定了黑色素瘤细胞系和组织中 KIF15 的表达水平。通过 MTT 和集落信息评估了 KIF15 对肿瘤发生的影响。通过流式细胞术检测了 KIF15 对细胞存活的功能。微阵列分析和生物信息学分析用于寻找 KIF15 的潜在靶标。我们表明 KIF15 在黑色素瘤细胞和组织中显著上调。在肿瘤中抑制 KIF15 显著降低了 A375 和 OCM1 细胞的肿瘤生长并增加了细胞凋亡。基于皮下异种移植模型的研究结果进一步与体外结果一致，即 KIF15 敲低抑制了体内黑色素瘤肿瘤的生长。微阵列分析和生物信息学表明 BIRC5、CDK4 和 WNT5A 是 KIF15 的三个潜在靶标。总之，我们的研究结果表明，KIF15 在黑色素瘤的致瘤性中发挥积极作用，它可能成为黑色素瘤，特别是葡萄膜黑色素瘤的新型诊断和治疗靶点。
