Effect of B7-homolog 4 on microRNA Expression Profile of Breast Cancer Cells
Objective This study aims to illustrate the mechanisms underlying the influence of im-munoregulatory molecule B7-homolog 4(B7-H4)on the immune escape and tumor progression through the miRNA expression profiles.Methods miRNA profiling was conducted using breast cancer cells with B7-H4 overexpression or knockout.Overlapping miRNAs were selected and then confirmed by qRT-PCR.We use TargetFinder and TargetScan web tools to identify the downstream target genes.To determine significantly enriched pathways,the target genes were subjected to gene ontology(GO)or Kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis.We further used the Kaplan-Meier plotter web tool to assess the impact of key miRNAs and target genes on the survival of breast cancer patients.Results B7-H4 knockout breast cancer cells showed significant alterations in 415 miRNAs,while B7-H4 overexpression resulted in significant alterations in 134 miRNAs.Overlapping analysis i-dentified 36 common miRNAs that exhibited consistent changes between the overexpression and knockout cell models.qRT-PCR analysis revealed 14 miRNAs that were associated with target genes involved in cell growth regulation and tumor metastasis,including TP53AIP1,RAD52,CDH7,FOXA1,CDH2 and ZEB1.Enrichment analysis showed that the target genes primarily participated in MAPK and Ras signa-ling pathways,suggesting their potential role in breast cancer progression.Conclusion Dysregulation of B7-H4 may change the expression of genes involved in tumor cell growth and metastasis through miRNA-dependent epigenetic regulation,thus affecting the progression and survival of patients with breast cancer.
breast cancermiRNAB7-homolog 4tumor metastasiscell proliferation
万方数据
维普
