Huo Yixuan, Zhang Wei, Yang Fan, Shao Wenhua, Cong Guozheng, Zhang Shoukai
First Clinical Medical College, Ningxia Medical University, Yinchuan, China.
Lanzhou University, Lanzhou, Gansu, China.
Front Oncol. 2025 Aug 1;15:1553626. doi: 10.3389/fonc.2025.1553626. eCollection 2025.
Abnormal activation of the hepatocyte growth factor (HGF) and c-mesenchymal-epithelial transition factor (c-Met) signaling pathway is associated with tumor occurrence and development. Serum HGF concentrations are significantly higher in patients with advanced and poorly differentiated laryngeal squamous cell carcinoma than those with early and highly differentiated disease. , a splice variant of HGF, can competitively bind to c-Met and acts as a specific antagonist of HGF. Although preliminary research has been conducted on the tumor-suppressing function of the gene, its specific mechanism of action in laryngeal cancer remains unclear.
Stable laryngeal squamous cell carcinoma cell lines expressing were developed using a lentiviral packaging method. The experimental group was labeled with PLV-NK4-TU212, whereas the control group was labeled with PLV-NC-TU212. Western blotting verified a stable expression. The functions of the molecule were assessed using MTT, EMT, and apoptosis assays, and cell lines were subjected to transcriptome sequencing.
Protein expression analysis showed that was stably expressed. Compared with the wild-type and negative control groups, overexpression of the gene inhibited the migration and proliferation of laryngeal squamous cell carcinoma cells and induced cell apoptosis. Transcriptome sequencing revealed that the expression levels of 320 genes differed significantly, with 189 upregulated and 131 downregulated genes.
In this study, a TU212 laryngeal squamous cell carcinoma cell line overexpressing was constructed using a lentiviral packaging system. Functional experiments showed that PLV-NK4-TU212 cells exhibited a significantly reduced migration rate, decreased proliferative ability, and increased apoptosis rate. The results of this study provide an experimental basis for as a potential therapeutic target for laryngeal squamous cell carcinoma highlighting its translational medical value.
肝细胞生长因子（HGF）和c-间充质-上皮转化因子（c-Met）信号通路的异常激活与肿瘤的发生和发展相关。晚期和低分化喉鳞状细胞癌患者血清HGF浓度显著高于早期和高分化患者。HGF的剪接变体NK4可竞争性结合c-Met，并作为HGF的特异性拮抗剂。虽然对NK4基因的抑癌功能已进行了初步研究，但其在喉癌中的具体作用机制仍不清楚。
采用慢病毒包装法构建稳定表达NK4的喉鳞状细胞癌细胞系。实验组标记为PLV-NK4-TU212，对照组标记为PLV-NC-TU212。蛋白质印迹法验证了稳定表达。使用MTT、EMT和凋亡试验评估NK4分子的功能，并对细胞系进行转录组测序。
蛋白质表达分析表明NK4稳定表达。与野生型和阴性对照组相比，NK4基因过表达抑制了喉鳞状细胞癌细胞的迁移和增殖，并诱导细胞凋亡。转录组测序显示320个基因的表达水平有显著差异，其中189个基因上调，131个基因下调。
本研究利用慢病毒包装系统构建了过表达NK4的TU212喉鳞状细胞癌细胞系。功能实验表明，PLV-NK4-TU212细胞的迁移率显著降低，增殖能力下降，凋亡率增加。本研究结果为NK4作为喉鳞状细胞癌的潜在治疗靶点提供了实验依据，突出了其转化医学价值。
