Abstract：
The mechanism by which DNMT3B facilitates esophageal cancer (ESCA) progression is currently unknown, despite its association with adverse prognoses in several cancer types. To investigate the potential therapeutic effects of the Chinese herbal medicine rhubarb on esophageal cancer (ESCA), we adopted an integrated bioinformatics approach. Gene Set Enrichment Analysis (GSEA) was first utilized to screen active anti-ESCA components in rhubarb. We then employed Weighted Gene Co-expression Network Analysis (WGCNA) to identify key molecular modules and targets related to the active components and ESCA pathogenesis. This system-level strategy integrating multi-omics data provides a powerful means to unravel the molecular mechanisms underlying the anticancer activities of natural products, like rhubarb. To investigate module gene functional enrichment, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. In addition, we evaluated the predictive impact of DNMT3B expression on ESCA patients utilizing the Kaplan-Meier method. Finally, we conducted experiments on cell proliferation and the cell cycle to explore the biological roles of DNMT3B. In this study, we identified Rhein as the main active ingredient of rhubarb that exhibited significant anti-ESCA activity. Rhein markedly suppressed ESCA cell proliferation. Utilizing Weighted Gene Co-expression Network Analysis (WGCNA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, we determined that the blue module was associated with Rhein target genes and the cell cycle. Additionally, DNMT3B was identified as a Rhein target gene. Analysis of The Cancer Genome Atlas (TCGA) database revealed that higher DNMT3B levels were associated with poor prognosis in ESCA patients. Furthermore, Rhein partially reversed the overexpression of DNMT3B to inhibit ESCA cell proliferation. In vitro studies demonstrated that Rhein and DNMT3B inhibition disrupted the S phase of the cell cycle and affected the production of cell cycle-related proteins. In this study, we found that Rhein exerts its anti-proliferative effects in ESCA cells by targeting DNMT3B and regulating the cell cycle.
摘要：
DNMT3B促进食管癌（ESCA）进展的机制目前尚不清楚，尽管它与几种癌症类型的不良预后有关。探讨中药大黄对食管癌的潜在治疗作用。我们采用了综合生物信息学方法。基因集富集分析（GSEA）首先用于筛选大黄中的活性抗ESCA成分。然后，我们采用加权基因共表达网络分析（WGCNA）来鉴定与活性成分和ESCA发病机理相关的关键分子模块和靶标。这种整合多组学数据的系统级策略为揭示天然产物抗癌活性的分子机制提供了强有力的手段。像大黄一样.为了研究模块基因功能富集，基因本体论（GO），和京都基因和基因组百科全书(KEGG)途径富集分析进行。此外,我们利用Kaplan-Meier方法评估了DNMT3B表达对ESCA患者的预测影响.最后,我们进行了细胞增殖和细胞周期的实验，以探讨DNMT3B的生物学作用。在这项研究中,我们确定大黄的主要活性成分是大黄，表现出显着的抗ESCA活性。大黄酸显著抑制ESCA细胞增殖。利用加权基因共表达网络分析（WGCNA）和京都基因和基因组百科全书（KEGG）分析，我们确定蓝色模块与Rhein靶基因和细胞周期相关。此外,DNMT3B被鉴定为大黄酸靶基因。对癌症基因组图谱（TCGA）数据库的分析显示，较高的DNMT3B水平与ESCA患者的不良预后相关。此外，大黄酸部分逆转DNMT3B的过表达以抑制ESCA细胞增殖。体外研究表明，大黄酸和DNMT3B抑制破坏了细胞周期的S期，并影响了细胞周期相关蛋白的产生。在这项研究中,我们发现大黄酸通过靶向DNMT3B和调节细胞周期在ESCA细胞中发挥抗增殖作用.
