Zhang Bo, Matsumoto Yoshihisa
Department of Transdisciplinary Science and Engineering, School of Environment and Society, Institute of Science Tokyo, Tokyo, Japan.
Laboratory for Zero-Carbon Energy, Institute of Integrated Research, Institute of Science Tokyo, Tokyo, Japan.
Cancer Rep (Hoboken). 2025 May;8(5):e70233. doi: 10.1002/cnr2.70233.
ZNF384 is a C2H2-type zinc finger protein (ZNF) which is implicated in DNA double-strand break (DSB) repair through the classical non-homologous end-joining (cNHEJ) pathway.
To clarify the regulatory mechanisms involving ZNF384 in colon adenocarcinoma (COAD).
First, we conducted a differential expression gene (DEG) analysis of mRNA and lncRNA using TCGA-COAD RNA-Seq data. We also identified ZNF384-related mRNAs through Pearson's correlation coefficient calculation and conducted weighted gene co-expression network analysis (WGCNA) for these genes, leading to the identification of a cluster of 331 genes with strongly positive correlation to tumor, 84 of which overlapped with DEGs. Gene functional analysis showed enrichment of genes in DNA repair, replication fork, and cell cycle checkpoint signaling pathways. Protein-protein interaction (PPI) network analysis of these 84 genes led to the identification of the top 20 key mRNAs. Then we employed three machine learning methods to refine our selection of candidate genes from these intersecting mRNAs. We constructed a competitive endogenous RNA (ceRNA) network and identified two significant intersecting miRNAs, miR-20b-5p and miR-424-5p, which have been shown to act as a tumor suppressor gene and an oncogene, respectively. Additionally, we found that KIF14 and KIF18B are regulated by these two miRNAs in this ceRNA network, particularly in DNA damage repair and cell cycle. Finally, validation using an external dataset from the GEO database confirmed their expression patterns.
The current study clarifies the mechanisms of how miR-20b-5p and miR-424-5p work in colon cancer and underscores their predictive capabilities in colon cancer.
ZNF384是一种C2H2型锌指蛋白（ZNF），通过经典的非同源末端连接（cNHEJ）途径参与DNA双链断裂（DSB）修复。
阐明ZNF384在结肠腺癌（COAD）中的调控机制。
首先，我们使用TCGA-COAD RNA-Seq数据对mRNA和lncRNA进行差异表达基因（DEG）分析。我们还通过计算Pearson相关系数鉴定了与ZNF384相关的mRNA，并对这些基因进行加权基因共表达网络分析（WGCNA），从而鉴定出一组与肿瘤呈强正相关的331个基因，其中84个与DEG重叠。基因功能分析显示这些基因在DNA修复、复制叉和细胞周期检查点信号通路中富集。对这84个基因进行蛋白质-蛋白质相互作用（PPI）网络分析，鉴定出前20个关键mRNA。然后，我们采用三种机器学习方法从这些相交的mRNA中优化候选基因的选择。我们构建了一个竞争性内源性RNA（ceRNA）网络，并鉴定出两个显著相交的miRNA，即miR-20b-5p和miR-424-5p，它们分别被证明可作为肿瘤抑制基因和癌基因发挥作用。此外，我们发现KIF14和KIF18B在这个ceRNA网络中受这两种miRNA调控，特别是在DNA损伤修复和细胞周期中。最后，使用来自GEO数据库的外部数据集进行验证，证实了它们的表达模式。
本研究阐明了miR-20b-5p和miR-424-5p在结肠癌中的作用机制，并强调了它们在结肠癌中的预测能力。
