目的:基于生物信息学分析TENM1在乳腺癌中的表达和预后价值和探究其对乳腺癌MDA-MB-231细胞的增殖和迁移的影响。方法:从TCGA数据库下载乳腺癌组织样本的TENM1表达谱进行差异表达分析;生存分析、单因素和多因素Cox回归分析以及构建Nomogram预测模型,以确认TENM1的独立预后价值;基因集富集分析评估与TENM1表达相关的失调信号通路;在乳腺癌MDA-MB-231细胞中干扰以及过表达TENM1后,CCK8与集落克隆实验检测细胞的增殖能力,Transwell实验检测细胞的迁移能力。结果:与正常样本相比,TENM1在乳腺癌组织中表达下调。生存分析、单因素和多因素Cox回归分析以及Nomogram预测模型提示TENM1可能是乳腺癌的独立预后因素。GSEA分析显示TENM1相关的信号通路在细胞分裂和细胞周期等差异富集。CCK8、集落克隆实验和Transwell实验结果显示沉默TENM1促进MDA-MB-231细胞的增殖和迁移能力,过表达TENM1则抑制其增殖和迁移能力。结论:TENM1在乳腺癌组织中表达下调,其可抑制乳腺癌MDA-MB-231细胞的增殖和迁移。TENM1可能作为乳腺癌的潜在预后分子标志物,并成为未来乳腺癌治疗的新靶点。
Objective:To study the bioinformatics-driven expression and prognostic significance of TENM1 in breast cancer (BRCA) and its effect on the proliferation and migration of MDA-MB-231 cells. Methods: TENM1 expression profiles of breast cancer tissue samples from the TCGA database were download for differential expression analysis. Survival analysis, univariate and multivariate Cox regression analysis were performed, and a Nomogram prediction model was established to validate the independent prognostic value of TENM1. Gene set enrichment analysis was used to evaluate dysregulated signaling pathways associated with TENM1 expression. After interfering and overexpressing TENM1 in MAD-MB-231 cells, proliferative capacity of cells was detected using CCK8 and clonogenic assays, and migratory capacity was detected using the Transwell migration assay. Results: TENM1 expression was decreased in breast cancer tissues comparing to normal samples. Results of survival analysis, univariate and multivariate Cox regression analysis and Nomogram prediction modeling indicated that TENM1 might be an independent prognostic factor for BRCA. GSEA analysis results showed that TENM1-related signaling pathways were selectively enriched at cell division and cell cycle. Suppression of TENM1 increased the proliferation and migration of MDA-MB-231 cells, as shown by CCK8, clonogenic assay and Transwell migration assay. Conversely, overexpression of TENM1 inhibited proliferation and migration. Conclusion: Down-regulated TENM1 expression is in breast cancer tissues could inhibit the proliferation and migration of MDA-MB-231 cells. TENM1 might be a valuable prognostic molecular marker for BRCA and a promising target for future treatment of BRCA .
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