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基于加权基因共表达网络分析(WGCNA)和机器学习算法预测生姜靶向蛋白精氨酸甲基转移酶1(PRMT1)/B细胞易位基因2(BTG2)轴抑制胃癌的分子机制

Predicting the molecular mechanism of ginger targeting PRMT1/BTG2 axis to inhibit gastric cancer based on WGCNA and machine algorithms.

作者信息

Chen Guoqing, Gou Boyun, Du Yuhua, Zhou Ziying, Bai Yuting, Yang Yi, Nan Yi, Yuan Ling

机构信息

College of Pharmacy, Ningxia Medical University, Yinchuan, 750004, Ningxia, China.

Department of pharmacy, General Hospital of Ningxia Medical University, Yinchuan, 750004, Ningxia Hui Autonomous Region, China.

出版信息

Phytomedicine. 2025 Jul 25;143:156892. doi: 10.1016/j.phymed.2025.156892. Epub 2025 May 24.

Abstract

OBJECTIVE

The aim of this study was to screen the biomarkers of ginger against gastric cancer (GC) by network pharmacology, WGCNA and machine algorithms. To find the upstream transcription factors and downstream signaling proteins constituting the signaling axis, so as to predict the possible mechanism of action of ginger against GC.

METHODS

Ginger was screened for active ingredients and targets through public databases. GC genes were screened using disease database, GEO database and WGCNA. The intersection of the four was taken to obtain the potential core genes. Machine algorithms was used to screen the core genes. Clinical relevance analysis, gene mutation relationship, epigenetic regulation analysis, immune infiltration analysis and molecular docking validation were performed on the core genes. Find its upstream transcription factors and downstream signaling proteins through database.

RESULTS

35 intersecting genes were obtained by databases and WGCNA analysis. Machine algorithms and PPI were combined to finally screen the core gene PRMT1. The upstream transcription factor of PRMT1 was identified as EGR1 and the downstream protein as BTG2 by database and molecular docking.

CONCLUSION

In this study, we found that PRMT1 could be used as a biomarker for ginger against GC using network pharmacology, WGCNA and machine algorithms. We hypothesized that ginger may exert antitumor effects through PRMT1/BTG2, providing new insights into the pharmacological mechanism of ginger against GC.

摘要

目的

本研究旨在通过网络药理学、加权基因共表达网络分析(WGCNA)和机器学习算法筛选生姜抗胃癌(GC)的生物标志物。寻找构成信号轴的上游转录因子和下游信号蛋白,以预测生姜抗GC的可能作用机制。

方法

通过公共数据库筛选生姜的活性成分和靶点。利用疾病数据库、基因表达综合数据库(GEO数据库)和WGCNA筛选GC相关基因。取四者的交集以获得潜在的核心基因。使用机器学习算法筛选核心基因。对核心基因进行临床相关性分析、基因突变关系分析、表观遗传调控分析、免疫浸润分析和分子对接验证。通过数据库查找其上游转录因子和下游信号蛋白。

结果

通过数据库和WGCNA分析获得35个交集基因。结合机器学习算法和蛋白质-蛋白质相互作用(PPI)最终筛选出核心基因蛋白精氨酸甲基转移酶1(PRMT1)。通过数据库和分子对接确定PRMT1的上游转录因子为早期生长反应蛋白1(EGR1),下游蛋白为BTG2。

结论

在本研究中,我们发现PRMT1可作为生姜抗GC的生物标志物。我们推测生姜可能通过PRMT1/BTG2发挥抗肿瘤作用,为生姜抗GC的药理机制提供了新的见解。

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