PDF(Pubmed)
Abstract：
In cancer cells, the nuclear transport system is often disrupted, leading to abnormal localization of nuclear proteins and altered gene expression. This disruption can arise from various mechanisms such as mutations in genes that regulate nuclear transport, altered expression of transport proteins, and changes in nuclear envelope structure. Oncogenic protein build-up in the nucleus due to the disturbance in nuclear transport can also boost tumor growth and cell proliferation. In this study, we performed bioinformatic analyses of 23 key nuclear transport receptors using genomic and transcriptomic data from pancancer and head and neck squamous cell carcinoma (HNSCC) datasets from The Cancer Genome Atlas (TCGA) and Cancer Cell Line Encyclopedia and found that the total alteration frequency of 23 nuclear transport receptors in 2691 samples of the PCAWG Consortium was 42.1% and a high levels of genetic alterations was significantly associated with poor overall survival. Amplification was the most common type of genetic alterations, and results in the overexpression of nuclear transport receptors in HNSCC compared to normal tissues. Furthermore, our study revealed that seven out of eight cell cycle genes (CDK1, CDK2, CDK4, CDK6, CCNA1, CCNB1, and CCNE2) were significantly and positively correlated with nuclear transport receptor genes in TCGA pancancer and CCLE datasets. Additionally, functional enrichment analysis showed that nuclear transport receptor genes were mainly enriched in the adhesion junction, cell cycle, ERBB, MAPK, MTOR and WNT signaling pathways.
摘要：
在癌细胞中，核运输系统经常中断，导致核蛋白的异常定位和基因表达的改变。这种破坏可能来自各种机制，例如调节核运输的基因突变，转运蛋白表达改变，和核包膜结构的变化。由于核转运的干扰而在细胞核中积聚的致癌蛋白也可以促进肿瘤生长和细胞增殖。在这项研究中,我们使用来自癌症基因组图谱(TCGA)和癌细胞系百科全书的癌症和头颈部鳞状细胞癌(HNSCC)数据集的基因组和转录组数据,对23个关键核转运受体进行了生物信息学分析,发现PCAWG联盟2691个样本中23个核转运受体的总改变频率为42.1%,高水平的遗传改变与不良的总体生存率显著相关。扩增是最常见的遗传改变类型，与正常组织相比，HNSCC中核转运受体的过表达。此外，我们的研究显示,8个细胞周期基因中的7个(CDK1,CDK2,CDK4,CDK6,CCNA1,CCNB1和CCNE2)与TCGA癌症和CCLE数据集中的核转运受体基因呈显著正相关.此外,功能富集分析表明,核转运受体基因主要富集在粘连连接处,细胞周期,ERBB,MAPK,MTOR和WNT信号通路。
