Zhao Li-Ming, Hong Wan-Ying, Xu Jian-Guang, Lin Shui-Quan, Liu Ming-Sheng, Wang Li-Hui, Jiang Xu-Li, Sang Ming, Lv Yang-Bo
Department of Gastroenterology, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou 324002, Zhejiang Province, China.
Department of Colorectal Surgery, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou 324002, Zhejiang Province, China.
World J Gastrointest Oncol. 2025 Jul 15;17(7):105264. doi: 10.4251/wjgo.v17.i7.105264.
Voltage-gated sodium channels (VGSCs, or Navs) are highly expressed in various tumors and play a critical role in tumor metastasis and invasion.
To identify Nav1.6-associated cancer genes through bioinformatics analysis and experimental validation, with the goal of determining the role of Nav1.6 in colorectal cancer (CRC) metastasis.
The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data were analyzed using weighted correlation network analysis (WGCNA) and Venn analysis to identify Nav1.6-associated genes in CRC. siRNA, real-time PCR, and western blotting were employed to validate the Nav1.6-associated cancer genes and signaling pathways identified in CRC. Cell counting kit-8 and Transwell migration assays were used to assess the proliferation and migration of CRC cells.
The analysis of TCGA and GEO datasets, along with WGCNA, identified 575 differentially expressed genes associated with (Nav1.6) in CRC, which were particularly enriched in MAPK signaling pathways. Tissue microarray analysis of surgical samples revealed elevated Nav1.6 levels in CRC tissues, which were predominantly in the cytoplasm and nucleus rather than in the membrane. Cytoplasmic Nav1.6 expression increased with T stage increases, consistent with the TCGA findings. knockdown in colon tumor cells significantly reduced cell proliferation and invasion and downregulated key proteins in the RAF-MAPK pathway.
These findings suggest that Nav1.6 promotes CRC cell proliferation and invasion which is related to the MAPK signaling pathway.
电压门控钠通道（VGSCs，或Navs）在多种肿瘤中高表达，在肿瘤转移和侵袭中起关键作用。
通过生物信息学分析和实验验证来鉴定与Nav1.6相关的癌症基因，以确定Nav1.6在结直肠癌（CRC）转移中的作用。
使用加权基因共表达网络分析（WGCNA）和韦恩分析对癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）数据进行分析，以鉴定CRC中与Nav1.6相关的基因。采用小干扰RNA（siRNA）、实时定量聚合酶链反应（real-time PCR）和蛋白质免疫印迹法来验证CRC中鉴定出的与Nav1.6相关的癌症基因和信号通路。使用细胞计数试剂盒-8（Cell counting kit-8）和Transwell迁移实验评估CRC细胞的增殖和迁移。
对TCGA和GEO数据集以及WGCNA的分析鉴定出CRC中575个与（Nav1.6）相关的差异表达基因，这些基因在丝裂原活化蛋白激酶（MAPK）信号通路中显著富集。手术样本的组织芯片分析显示CRC组织中Nav1.6水平升高，主要位于细胞质和细胞核而非细胞膜。细胞质Nav1.6表达随T分期增加而增加，与TCGA结果一致。结肠肿瘤细胞中（基因名称缺失）敲低显著降低细胞增殖和侵袭，并下调RAF-MAPK通路中的关键蛋白。
这些发现表明Nav1.6促进CRC细胞增殖和侵袭，这与MAPK信号通路有关。
