Regulation of DZIP1 Expression in CAFs by Jianpi Yangzheng Xiaozheng Formula and Its Impact on Mesenchymal Characteristics of Diffuse Gastric Cancer
10.13422/j.cnki.syfjx.20250518
- VernacularTitle:健脾养正消癥方通过干预CAFs中DZIP1表达影响弥漫型胃癌间充质特征
- Author:
Yuanjie LIU
1
;
Qianwen YE
1
;
Xi ZOU
1
Author Information
1. Affiliated Hospital of Nanjing University of Chinese Medicine， Nanjing 210029，China
- Publication Type:Journal Article
- Keywords:
Jianpi Yangzheng Xiaozheng formula;
transcriptomics;
diffuse gastric cancer;
DAZ interacting protein 1 （DZIP1）;
epithelial-mesenchymal transition
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(21):90-101
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo establish a subcutaneous xenograft model of gastric cancer in nude mice and to identify differentially expressed genes （DEGs） affected by Jianpi Yangzheng Xiaozheng formula （JPYZXZ） in diffuse gastric cancer （DGC） using transcriptome sequencing. The study aims to identify potential key prognostic factors and preliminarily elucidate the therapeutic mechanism of JPYZXZ. MethodsSubcutaneous tumor tissues were collected from nude mice treated with JPYZXZ （6 g·kg-1）and from the untreated traditional Chinese medicine control group. High-throughput RNA sequencing was performed to extract and analyze total RNA and identify DEGs， followed by functional enrichment analysis. DEGs were intersected with cancer-associated fibroblast （CAF）-related genes identified from single-cell RNA sequencing （scRNA-seq） data. A Cox proportional hazards regression model （Cox model） was constructed to identify potential key targets， among which DAZ interacting protein 1 （DZIP1） was selected. The role of DZIP1 in DGC progression was further verified through in vitro and in vivo experiments. ResultsTranscriptome sequencing revealed that DEGs regulated by JPYZXZ were significantly enriched in biological processes such as focal adhesion， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway， and vascular development （P<0.05）. Intersection analysis with CAF marker genes identified ten potential common target genes. Cox regression analysis combined with the Cancer Genome Atlas （TCGA） dataset for stomach adenocarcinoma （STAD） confirmed that DZIP1 is an independent prognostic factor significantly associated with poor outcomes. Transcriptome and immunohistochemical analyses showed that DZIP1 expression was significantly higher in gastric cancer tissues than in adjacent tissues， while JPYZXZ treatment downregulated DZIP1 expression in a dose-dependent manner. Clinical data further demonstrated that serum DZIP1 levels in patients treated with JPYZXZ were significantly lower than those in the control group. ConclusionJPYZXZ may inhibit the malignant progression of DGC by downregulating DZIP1 expression， thereby suppressing CAF activation and epithelial-mesenchymal transition （EMT）. These findings provide experimental evidence and identify DZIP1 as a potential therapeutic target in DGC treatment.
