Tsai Hsing-Fang, Chang Yu-Chan, Li Chien-Hsiu, Chan Ming-Hsien, Chen Chi-Long, Tsai Wen-Chiuan, Hsiao Michael
Genomics Research Center, Academia Sinica, Taipei, Taiwan.
Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Cell Death Discov. 2021 Oct 26;7(1):313. doi: 10.1038/s41420-021-00661-3.
Glioblastoma (GBM) is a fatal cancer. Existing therapies do not have significant efficacy for GBM patients. Previous studies have shown that the collagen family is involved in the regulation of the extracellular environment of cancer cells, and these conditions could become an important factor for effective treatment. Therefore, we screened various collagen types and observed that the type V collagen α1 chain (COL5A1) gene plays a pivotal role in GBM. We further examined whether the overexpression of COL5A1 is common in mesenchymal subtypes and is related to the survival rate of GBM patients through several in silico cohorts. In addition, our cohort also showed a consistent trend in COL5A1 protein levels. Most importantly, we validated the cell mobility, metastatic ability and actin polymerization status caused by COL5A1 with two-way models. Based on these results, we established a transcriptomics dataset based on COL5A1. Moreover, PPRC1, GK and ESM1 were predicted by ingenuity pathway analysis (IPA) to be transcription factors or to participate downstream. We investigated the involvement of COL5A1 in extracellular remodeling and the regulation of actin filaments in the metastasis of GBM. Our results indicate that the COL5A1-PPRC1-ESM1 axis may represent a novel therapeutic target in GBM.
胶质母细胞瘤(GBM)是一种致命的癌症。现有疗法对GBM患者没有显著疗效。先前的研究表明,胶原蛋白家族参与癌细胞外环境的调节,而这些情况可能成为有效治疗的重要因素。因此,我们筛选了各种胶原蛋白类型,观察到V型胶原蛋白α1链(COL5A1)基因在GBM中起关键作用。我们通过几个计算机模拟队列进一步研究了COL5A1的过表达在间充质亚型中是否常见以及是否与GBM患者的生存率相关。此外,我们的队列在COL5A1蛋白水平上也显示出一致的趋势。最重要的是,我们用双向模型验证了由COL5A1引起的细胞迁移、转移能力和肌动蛋白聚合状态。基于这些结果,我们建立了一个基于COL5A1的转录组学数据集。此外,通过 Ingenuity 通路分析(IPA)预测PPRC1、GK和ESM1为转录因子或参与下游过程。我们研究了COL5A1在GBM转移过程中参与细胞外重塑和肌动蛋白丝调节的情况。我们的结果表明,COL5A1-PPRC1-ESM1轴可能代表GBM中的一个新的治疗靶点。