Hernández-Nava Elizabeth, Montaño Luis F, Rendón-Huerta Erika P
Laboratorio Inmunobiología, Departamento Biología Celular y Tisular, Facultad de Medicina, UNAM, Mexico City, Mexico.
J Oncol. 2021 Dec 18;2021:5936905. doi: 10.1155/2021/5936905. eCollection 2021.
Gastric cancer is a heterogeneous disease that represents 5% to 10% of all new cancer cases worldwide. Advances in histological diagnosis and the discovery of new genes have admitted new genomic classifications. Nevertheless, the bioinformatic analysis of gastric cancer databases has favored the detection of specific differentially expressed genes with biological significance. Claudins, a family of proteins involved in tight junction physiology, have emerged as the key regulators of cellular processes, such as growth, proliferation, and migration, associated with cancer progression. The expression of Claudin-9 in the gastric cancer tissue has been linked to poor prognosis, however, its transcriptional and epigenetic regulations demand a more comprehensive analysis. Using the neural network promoter prediction, TransFact, Uniprot-KB, Expasy-SOPMA, protein data bank, proteomics DB, Interpro, BioGRID, String, and the FASTA protein sequence databases and software, we found the following: (1) the promoter sequence has an unconventional structure, including different transcriptional regulation elements distributed throughout it, (2) GATA 4, GATA 6, and KLF5 are the key regulators of Claudin-9 expression, (3) Oct1, NF-B, AP-1, c-Ets-1, and HNF-3 have the higher binding affinity to the CLDN9 promoter, (4) Claudin-9 interacts with cell differentiation and development proteins, (5) CLDN9 is highly methylated, and (6) Claudin-9 expression is associated with poor survival. In conclusion, Claudin-9 is a protein that should be considered a diagnostic marker as its gene promoter region binds to the transcription factors associated with the deregulation of cell control, enhanced cell proliferation, and metastasis.
胃癌是一种异质性疾病，占全球所有新发癌症病例的5%至10%。组织学诊断的进展和新基因的发现促成了新的基因组分类。然而，对胃癌数据库的生物信息学分析有助于检测具有生物学意义的特定差异表达基因。紧密连接蛋白家族Claudins是参与紧密连接生理过程的蛋白质，已成为与癌症进展相关的细胞过程（如生长、增殖和迁移）的关键调节因子。Claudin-9在胃癌组织中的表达与预后不良有关，但其转录和表观遗传调控需要更全面的分析。使用神经网络启动子预测工具TransFact、Uniprot-KB、Expasy-SOPMA、蛋白质数据库、蛋白质组学数据库、Interpro、BioGRID、String以及FASTA蛋白质序列数据库和软件，我们发现：（1）启动子序列具有非常规结构，包括分布在其中的不同转录调控元件；（2）GATA 4、GATA 6和KLF5是Claudin-9表达的关键调节因子；（3）Oct1、NF-κB、AP-1、c-Ets-1和HNF-3与CLDN9启动子具有更高的结合亲和力；（4）Claudin-9与细胞分化和发育蛋白相互作用；（5）CLDN9高度甲基化；（6）Claudin-9表达与较差的生存率相关。总之，Claudin-9是一种应被视为诊断标志物的蛋白质，因为其基因启动子区域与细胞控制失调、细胞增殖增强和转移相关的转录因子结合。
