Department of Cancer Immunology, Chair of Medical Biotechnology, Poznan University of Medical Sciences, 8 Rokietnicka Street, 60-806 Poznan, Poland.
Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Center, 15 Garbary Street, 61-866 Poznan, Poland.
Int J Mol Sci. 2023 Nov 15;24(22):16380. doi: 10.3390/ijms242216380.
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.
全球癌症负担仍然很高；因此，需要更好地了解驱动致癌作用的分子机制，以改善当前的预防和治疗选择。我们之前在多种肿瘤中检测到 ZNF643/ZFP69B 基因上调，并推测它可能在肿瘤生物学中发挥作用。为了验证这一假设，我们利用 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 分析和体外研究，评估了癌细胞表型，并寻找 ZNF643 结合的基因组位点。我们的数据表明，与正常样本相比，大多数分析的肿瘤中 ZNF643 的水平更高，这可能是由于拷贝数变异。ZNF643 mRNA 与不同的分子和免疫亚型以及临床病理特征（肿瘤分期、分级、患者生存）相关。RNA-seq 分析显示，ZNF643 沉默会引发与各种癌症相关过程（如生长、粘附和免疫系统）相关的基因失调。此外，我们观察到 ZNF643 正向影响细胞周期、迁移和侵袭。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，并指出了它对细胞粘附和免疫过程的影响。
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