Mesoderm Development-related Genes and Signaling Pathways Affect the Occurrence and Development of Melanoma
10.13865/j.cnki.cjbmb.2025.06.1061
- VernacularTitle:中胚层发育关键基因和信号通路影响皮肤黑色素瘤的发生发展
- Author:
Jia-Xin MA
1
;
Zhi-Dong GUO
;
Yun-Bin ZHANG
;
Ming YAO
Author Information
1. 宁夏医科大学总医院烧伤整形美容科,宁夏回族自治区,银川 750001
- Publication Type:Journal Article
- Keywords:
skin cutaneous melanoma(SKCM);
mesodermal development;
bioinformatics analysis;
TGF-β signaling pathway;
epithelial-mesenchymal transition(EMT);
immune microenvironment
- From:
Chinese Journal of Biochemistry and Molecular Biology
2025;41(8):1179-1192
- CountryChina
- Language:Chinese
-
Abstract:
This study systematically investigated the molecular mechanisms underlying the involvement of mesoderm development-associated genes in melanoma progression through integrated bioinformatics analy-sis and experimental validation.Utilizing the GSVA(gene set variation analysis)algorithm to perform enrichment analysis of 7 752 biological functions in 406 skin cutaneous melanoma(SKCM)cases,we i-dentified for the first time the significant activation of mesoderm development pathways during SKCM pathogenesis.Four core regulatory genes(SMAD4,NODAL,BMPR1A,and ZFP36L1)were screened using LASSO-COX regression analysis and a prognostic risk-scoring system was established.Gene Ontolo-gy(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses revealed predomi-nant enrichment of these genes in mRNA metabolic processes and TGF-β signaling pathways.Experimen-tal validation through Quantitative Polymerase Chain Reaction(qPCR),Western blotting,and immuno-histochemistry(IHC)demonstrated that:(1)Downregulation of SMAD4 and BMPR1A in tumor tissues was significantly correlated with poor prognosis(P＜0.05);(2)NODAL promoted tumor invasion and metastasis by regulating epithelial-mesenchymal transition(EMT);(3)High ZFP36L1 expression was associated with enhanced chemotherapy sensitivity.Further analyses revealed significant correlations be-tween core gene expression levels and tumor immune infiltration characteristics as well as immune check-point molecules.By integrating multi-omics analysis with experimental validation,this study elucidates the critical roles of mesoderm development-associated genes in SKCM progression,particularly clarifying the molecular mechanisms through which SMAD4/NODAL/BMPR1A/ZFP36L1 influence tumor biologi-cal behaviors via immune microenvironment regulation and EMT processes.These findings provide novel theoretical foundations for molecular subtyping and targeted therapy in melanoma.
