全球癌症负担仍然很高;因此,需要更好地了解驱动癌变的分子机制,以改进当前的预防和治疗方案.我们先前检测到ZNF643/ZFP69B基因在多种肿瘤中上调,我们推测它可能在肿瘤生物学中起作用。为了检验这个假设,我们使用以TCGA为中心的数据库将ZNF643状态与各种临床病理参数相关联.我们还进行了RNA-seq分析和评估癌细胞表型的体外研究,我们搜索了ZNF643结合的基因组基因座。我们的数据表明,与正常样本相比,大多数分析肿瘤中的ZNF643水平更高,可能是由于拷贝数变化。ZNF643mRNA与不同的分子和免疫亚型以及临床病理特征(肿瘤分期,grade,患者生存)。RNA-seq分析显示,ZNF643沉默会触发参与各种癌症相关过程的基因失调,比如增长,附着力,和免疫系统。此外,我们观察到ZNF643正向影响细胞周期,迁移,和入侵。最后,我们的ChIP-seq分析表明与ZNF643结合相关的基因与粘附和免疫信号有关。总之,我们的数据证实了ZNF643的致癌特性,并指出了其对细胞粘附和免疫过程的影响。
The global cancer burden remains high; thus, a better understanding of the molecular mechanisms driving carcinogenesis is needed to improve current prevention and treatment options. We previously detected the ZNF643/ZFP69B gene upregulated in multiple tumors, and we speculated it may play a role in tumor biology. To test this hypothesis, we employed TCGA-centered databases to correlate ZNF643 status with various clinicopathological parameters. We also performed RNA-seq analysis and in vitro studies assessing cancer cell phenotypes, and we searched for ZNF643-bound genomic loci. Our data indicated higher levels of ZNF643 in most analyzed tumors compared to normal samples, possibly due to copy number variations. ZNF643 mRNA correlated with diverse molecular and immune subtypes and clinicopathological features (tumor stage, grade, patient survival). RNA-seq analysis revealed that ZNF643 silencing triggers the deregulation of the genes implicated in various cancer-related processes, such as growth, adhesion, and immune system. Moreover, we observed that ZNF643 positively influences cell cycle, migration, and invasion. Finally, our ChIP-seq analysis indicated that the genes associated with ZNF643 binding are linked to adhesion and immune signaling. In conclusion, our data confirm the oncogenic properties of ZNF643 and pinpoint its impact on cell adhesion and immune processes.