中国肿瘤生物治疗杂志2025，Vol.32Issue(7)：716-722,7.DOI:10.3872/j.issn.1007-385x.2025.07.006
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
Mechanism of bexarotene in suppressing double hit lymphoma via modulation of the c-Myc pathway:Insights from WGCNA
摘要
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.关键词
双打击淋巴瘤/贝沙罗汀/基于加权基因共表达网络分析/生物标志物/分子机制Key words
double hit lymphoma(DHL)/bexarotene/Weighted Gene Co-expression Network Analysis(WGCNA)/biomarker/molecular mechanism分类
医药卫生引用本文复制引用
何田田,李泓毅,耿杰,侯传东,张虹,张辉,赵鹏,卢学春,贺培风..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[J].中国肿瘤生物治疗杂志,2025,32(7):716-722,7.基金项目
国家老年疾病临床医学研究中心多中心RCT临床研究项目(No.NCRCG-PLAGH-20230010) （No.NCRCG-PLAGH-20230010）
军队后勤保健课题(No.23BJZ25) （No.23BJZ25）
国家自然科学基金(No.72474125) （No.72474125）
