Mechanism of bexarotene in suppressing double hit lymphoma via modulation of the c-Myc pathway:Insights from WGCNA
10.3872/j.issn.1007-385x.2025.07.006
- VernacularTitle:基于WGCNA揭示贝沙罗汀通过调控c-Myc通路抑制双打击淋巴瘤的机制
- Author:
Tiantian HE
1
;
Hongyi LI
;
Jie GENG
;
Chuandong HOU
;
Hong ZHANG
;
Hui ZHANG
;
Peng ZHAO
;
Xuechun LU
;
Peifeng HE
Author Information
1. 山西医科大学 医学科学院,山西 太原 030001
- Publication Type:Journal Article
- Keywords:
double hit lymphoma(DHL);
bexarotene;
Weighted Gene Co-expression Network Analysis(WGCNA);
biomarker;
molecular mechanism
- From:
Chinese Journal of Cancer Biotherapy
2025;32(7):716-722
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the molecular mechanisms of bexarotene in treating double hit lymphoma(DHL)based on Weighted Gene Co-expression Network Analysis(WGCNA),thereby providing potential targets and experimental evidence for DHL treatment.Methods:The gene expression datasets GSE44164 and GSE43677 were downloaded from the Gene Expression Omnibus(GEO)database,and differentially expressed genes(DEGs)were identified.WGCNA was employed to identify gene modules associated with DHL.A protein-protein interaction(PPI)network was constructed to screen for key hub genes.Drug-gene association analysis was conducted using the EpiMed platform to identify potential targeted drugs for DHL.The effects of bexarotene on DHL cell proliferation and key protein expression were evaluated using the CCK-8 assay and Western blotting(WB),and its effects on cell apoptosis was evaluated using flow cytometry.Results:WGCNA identified a turquoise module highly associated with DHL,and 10 hub genes(COL1A2,COL3A1,MMP2,COL5A2,DCN,BGN,FN1,MMP9,FBN1,and LUM)were screened from the PPI network.Drug association analysis nominated bexarotene as a potential therapeutic agent.In vitro validation demonstrated that bexarotene significantly inhibited U2932 cell viability(P<0.05),promoted cell apoptosis(P<0.001),and downregulated c-Myc and COL1A2 expression(P<0.05).Conclusion:Bexarotene may exert anti-DHL effects by suppressing the c-Myc signaling pathway and modulating extracellular matrix-related genes.Further studies are warranted to validate its in vivo efficacy and potential for combination therapy.
