Identifying biomarkers for the early diagnosis of glioma and elucidating the molecular mechanisms underlying the development of this cancer are of considerable clinical importance. Recently, studies performing microarray profiling of genes to identify distinct gene signatures reported specific subtypes with predictive and prognostic relevance. Thus, we performed deep sequencing on a total of 26 glioma tissue samples to identify the frequently mutated of oncogenes and tumor suppressors in gliomas. A total of 2306 single-nucleotide polymorphisms (SNPs) and 2010 insertion and deletion sites (indels) were found by aligning sequencing information from 26 glioma samples with sequences from the normal human gene database (GRCh37/hg19). GSEA results suggest that an underexpressed gene, calmodulin binding transcription activator 1 (CAMTA1), participates in the cell proliferation and cell cycle regulation of glioma cells. Moreover, overexpression of CAMTA1 in glioma cells notably inhibited cell growth, migration, invasion and cell cycle and enhanced temozolomide (TMZ)-induced cell apoptosis in glioma cells, while CAMTA1 overexpression decreased the ITGA5, ITGB1, p-AKT, p-FAK, and Myc protein levels, suggesting that the signaling pathways of these proteins might be involved in the cellular functions of CAMTA1 in glioma. Moreover, overexpression of CAMTA1 attenuated the growth and tumorigenesis of glioma in vivo. In summary, we identified high-frequency mutant genes in glioma and provided an experimental basis for a novel mechanism by which CAMTA1 may serve as a tumor suppressor in glioma.

识别早期诊断胶质瘤的生物标志物并阐明这种癌症发展的分子机制具有相当大的临床意义。最近，进行基因微阵列分析以识别不同基因特征的研究报告了具有预测和预后相关性的特定亚型。因此，我们对总共 26 个胶质瘤组织样本进行了深度测序，以识别胶质瘤中经常突变的癌基因和肿瘤抑制基因。通过将来自 26 个神经胶质瘤样本的测序信息与来自正常人类基因数据库 (GRCh37/hg19) 的序列进行比对，共发现了 2306 个单核苷酸多态性 (SNP) 和 2010 个插入和缺失位点 (indel)。GSEA 结果表明表达不足的基因，钙调蛋白结合转录激活因子 1 (CAMTA1)，参与胶质瘤细胞的细胞增殖和细胞周期调控。此外，CAMTA1 在胶质瘤细胞中的过表达显着抑制了细胞生长、迁移、侵袭和细胞周期，并增强了替莫唑胺 (TMZ) 诱导的胶质瘤细胞凋亡，而 CAMTA1 过表达降低了 ITGA5、ITGB1、p-AKT、p-FAK、和 Myc 蛋白水平，表明这些蛋白的信号通路可能参与胶质瘤中 CAMTA1 的细胞功能。此外，CAMTA1的过表达减弱了胶质瘤的生长和肿瘤发生 而 CAMTA1 过表达降低了 ITGA5、ITGB1、p-AKT、p-FAK 和 Myc 蛋白水平，表明这些蛋白的信号通路可能参与了 CAMTA1 在胶质瘤中的细胞功能。此外，CAMTA1的过表达减弱了胶质瘤的生长和肿瘤发生 而 CAMTA1 过表达降低了 ITGA5、ITGB1、p-AKT、p-FAK 和 Myc 蛋白水平，表明这些蛋白的信号通路可能参与了 CAMTA1 在胶质瘤中的细胞功能。此外，CAMTA1的过表达减弱了胶质瘤的生长和肿瘤发生在体内。总之，我们鉴定了胶质瘤中的高频突变基因，并为CAMTA1可能作为胶质瘤中的肿瘤抑制因子的新机制提供了实验基础。