CLK2基因在结肠腺癌患者中的表达变化及其对结肠腺癌细胞功能的调控

Changes in CLK2 Gene Expression in Patients with Colon Adenocarcinoma and Its Regulation of Colon Adenocarcinoma Cell Function

摘要: 目的：评估不同阶段结肠腺癌患者中CDC样激酶2 (CLK2)基因的表达，以及CLK2在结肠腺癌细胞中的表达变化和CLK2所介导的细胞功能。方法：在TIMER数据库和GEPIA数据库分析CLK2在健康与不同肿瘤组织中的表达水平，找到差异性表达显著的肿瘤类型。分析TCGA数据库中各个阶段结肠腺癌患者组织中CLK2的表达水平变化。使用RT-qPCR和western blot方法检测了CLK2基因在肿瘤组织和细胞系中的表达变化。在敲低CLK2的条件下，使用western blot方法检测细胞增殖标志物和细胞周期标志物的表达。最后，使用STRING工具分析与CLK2基因相关性较强的多个关键基因。结果：结肠腺癌组织中的CLK2基因表达显著升高(p < 0.001)，并且CLK2基因的高表达与结肠腺癌的临床特征(病理分期，T分期)显著相关(p < 0.05)。CLK2基因在结肠腺癌细胞中表达升高，敲低CLK2的表达能够有效抑制细胞增殖和细胞周期。最后检测到CLK3、CLK1、SRSF12等基因是CLK2基因的潜在结合靶点。结论：CLK2基因的表达水平与结肠腺癌发生的进程显著相关，降低CLK2基因的表达，有望成为结肠腺癌患者治疗的新方式。

Abstract: Objective: To assess CDC-like kinase 2 (CLK2) gene expression in patients with different stages of colon adenocarcinoma, as well as changes in CLK2 expression in colon adenocarcinoma cells and cellular functions mediated by CLK2. Methods: Screening for CLK2 differentially expressed tumor types in the TIMER database and the GEPIA database. Detection of CLK2 gene changes with colon adenocarcinoma tumor stage in the TCGA database. Changes in CLK2 gene expression in tumor tissues and cell lines were detected using RT-qPCR and western blot methods. The expressions of cell proliferation markers and cell cycle markers were detected using western blot method under the condition of knocking down CLK2. Finally, multiple key genes with strong correlation with CLK2 gene were analyzed using STRING tool. Results: CLK2 gene expression was significantly elevated in colon adenocarcinoma tissues (p < 0.001), and the high expression of CLK2 gene was significantly correlated with the clinical features of colon adenocarcinoma (pathological stage, T stage) (p < 0.05). CLK2 gene expression is elevated in colon adenocarcinoma cells, and knockdown of CLK2 expression can effectively inhibit cell proliferation and cell cycle. Finally, CLK3, CLK1, SRSF12 and other genes are potential binding targets of CLK2 gene. Conclusion: The expression level of the CLK2 gene is significantly correlated with the progression of colon adenocarcinoma, and decreasing the expression of the CLK2 gene is expected to be a new approach to the treatment of patients with colon adenocarcinoma.