Department of Dermatology, School of Clinical Medicine, Shandong University, Jinan, Shandong, China.
Department of Dermatology, The Fourth Hospital of Jinan, Jinan, Shandong, China.
J Biochem Mol Toxicol. 2019 Dec;33(12):e22409. doi: 10.1002/jbt.22409. Epub 2019 Oct 16.
Melanoma is the most aggressive type of cutaneous tumor and the occurrence of metastasis makes it resistant to almost all available treatment and becomes incorrigible. Hence, identifying metastasis-related biomarkers and effective therapeutic targets will assist in preventing metastasis and ameliorating cutaneous melanoma. In our present study, we reported kinesin family member 18B (KIF18B) as a novel contributor in cutaneous melanoma proliferation and metastasis, and it was found to be of great significance in predicting the prognosis of cutaneous melanoma patients. Bioinformatics analysis based on ONCOMINE, The Cancer Genome Atlas, and Genotype-Tissue Expression database revealed that KIF18B was highly expressed in cutaneous melanoma and remarkably correlated with unfavorable clinical outcomes. Consistently, the results of the quantitative real-time polymerase chain reaction exhibited that the expression of KIF18B was significantly higher in cutaneous melanoma cell lines than that in normal cells. In vitro, biological assays found that knockdown of KIF18B in cutaneous melanoma cells noticeably repressed cell proliferation, migration, and invasion, while inducing cell apoptosis. Moreover, the protein expression of E-cadherin was enhanced while the expression of N-cadherin, vimentin, and Snail was decreased in M14 cells after knocking down KIF18B. In addition, the phosphorylation of phosphoinositide 3-kinase (PI3K) and extracellular-signal-regulated kinase (ERK) was significantly suppressed in M14 cells with silenced KIF18B. Above all, our results indicated that the repression of cutaneous melanoma cell migration and proliferation caused by KIF18B depletion suggested an oncogenic role of KIF18B in cutaneous melanoma, which acts through modulating epithelial-mesenchymal transition and ERK/PI3K pathway.
黑色素瘤是最具侵袭性的皮肤肿瘤类型，其转移的发生使其对几乎所有可用的治疗方法都具有抗性，且无法治愈。因此，确定与转移相关的生物标志物和有效的治疗靶点将有助于预防转移和改善皮肤黑色素瘤。在本研究中，我们报道了驱动蛋白家族成员 18B（KIF18B）是皮肤黑色素瘤增殖和转移的新贡献者，它在预测皮肤黑色素瘤患者的预后方面具有重要意义。基于 ONCOMINE、癌症基因组图谱和基因型组织表达数据库的生物信息学分析表明，KIF18B 在皮肤黑色素瘤中高度表达，并与不良的临床结局显著相关。一致地，定量实时聚合酶链反应的结果表明，KIF18B 在皮肤黑色素瘤细胞系中的表达明显高于正常细胞。在体外，生物学测定发现，敲低皮肤黑色素瘤细胞中的 KIF18B 明显抑制细胞增殖、迁移和侵袭，同时诱导细胞凋亡。此外，在敲低 KIF18B 后，M14 细胞中 E-钙黏蛋白的蛋白表达增强，而 N-钙黏蛋白、波形蛋白和 Snail 的表达减少。此外，沉默 KIF18B 的 M14 细胞中磷酸肌醇 3-激酶（PI3K）和细胞外信号调节激酶（ERK）的磷酸化显著受到抑制。总之，我们的结果表明，KIF18B 耗竭导致皮肤黑色素瘤细胞迁移和增殖受到抑制，提示 KIF18B 在皮肤黑色素瘤中具有致癌作用，通过调节上皮-间充质转化和 ERK/PI3K 通路发挥作用。
