School of Medicine, Nantong University, Nantong, China.
Department of General Surgery, Yancheng Third People's Hospital, Yancheng, China.
Pediatr Hematol Oncol. 2022 Mar;39(2):145-157. doi: 10.1080/08880018.2021.1953655. Epub 2021 Aug 11.
Emerging evidence suggests that KIF11 could play a pivotal role in cancer cell proliferation; however, its biological functions and molecular mechanisms in Wilms tumor (WT) cells are largely unknown. The aim of this study was to evaluate the clinical significance and therapeutic potential of KIF11 proteins in WT. KIF11 expression in WT tissues and adjacent nontumor tissues was determined using qRT-PCR, Western blotting, immunohistochemistry (IHC) and bioinformatics. The function of KIF11 protein was determined by its correlation with tumor cell growth, angiogenesis, and apoptosis using IHC and lentiviral vector-mediated KIF11 depletion. KIF11 expression was upregulated in WT tissues and was associated with WT clinical outcomes. Tumor KIF11 expression was significantly associated with the Ki67 proliferation index. CCK-8, flow-cytometric analysis, and Western blotting revealed that KIF11 knockdown significantly inhibited WT cell growth. Functional studies have indicated that increased KIF11 expression is significantly correlated with vascular endothelial growth factor (VEGF) expression and intratumoral microvessel density. We further confirmed that downregulated expression of KIF11 promoted cell apoptosis and significantly increased Bcl-2 and Bax expression. Our findings demonstrate that KIF11 plays a role in promoting the development of human WT and can serve as a potential molecular marker for the treatment of WT.
新出现的证据表明，KIF11 可能在癌细胞增殖中发挥关键作用；然而，其在Wilms 瘤（WT）细胞中的生物学功能和分子机制在很大程度上仍是未知的。本研究旨在评估 KIF11 蛋白在 WT 中的临床意义和治疗潜力。通过 qRT-PCR、Western blot、免疫组织化学（IHC）和生物信息学检测 WT 组织和相邻非肿瘤组织中的 KIF11 表达。通过 IHC 和慢病毒载体介导的 KIF11 耗竭来确定 KIF11 蛋白的功能，其与肿瘤细胞生长、血管生成和细胞凋亡有关。WT 组织中 KIF11 表达上调，并与 WT 临床结局相关。肿瘤 KIF11 表达与 Ki67 增殖指数显著相关。CCK-8、流式细胞术分析和 Western blot 显示，KIF11 敲低显著抑制 WT 细胞生长。功能研究表明，KIF11 表达增加与血管内皮生长因子（VEGF）表达和肿瘤内微血管密度显著相关。我们进一步证实，下调 KIF11 表达促进细胞凋亡，并显著增加 Bcl-2 和 Bax 表达。我们的研究结果表明，KIF11 在促进人类 WT 的发展中发挥作用，可作为 WT 治疗的潜在分子标志物。
