{"title":"Bioinformatics analysis identifies dysregulation of miR-548F-3p and its hub gene in triple-negative breast cancer.","authors":"Samira Behroozi, Mahdieh Salimi, Najaf Allahyari Fard","doi":"10.22038/ijbms.2025.79808.17287","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>Triple-negative breast cancer (TNBC), which affects 15-20% of cases, lacks targeted therapies and poses challenges in treatment. MicroRNAs (miRNAs) are potential biomarkers and therapeutic targets in breast cancer. To unravel its unique regulatory role, this study focused on miRNA microarray analysis, particularly miR-548F-3p, in TNBC samples.</p><p><strong>Materials and methods: </strong>Using the GSE76275 dataset, gene expression profiles were analyzed using the Affymetrix Human Genome U133 Plus 2.0 Array. Differentially expressed genes (DEGs) were identified using robust preprocessing. Weighted gene co-expression network analysis (WGCNA) explored gene modules and identified hub genes co-expressed with miR-548F-3p. Functional enrichment and protein-protein interaction (PPI) network analyses were conducted. Survival analysis was used to assess the prognostic impact of the identified genes.</p><p><strong>Results: </strong>The study found 224 up-regulated DEGs, with miR-548F-3p exhibiting significant down-regulation. MultimiR identified 400 genes that were targeted by miR-548F-3p. WGCNA revealed a blue co-expression module, with 356 genes targeted by miR-548F-3p. A Venn diagram identified common genes, including VANGL2, BRCC3, ANP32E, and ANLN. Functional enrichment highlighted crucial pathways in TNBC pathogenesis, including mitotic spindle organization, spindle assembly checkpoint signaling, cell cycle, and amino acid (serine) metabolism. PPI network analysis identified hub genes, including FOXM1, KIF23, and CDC20. VANGL2, BRCC3, ANP32E, and ANLN were significantly associated with patient outcomes in survival analysis.</p><p><strong>Conclusion: </strong>This analysis highlighted TNBC's molecular landscape, emphasizing miR-548F-3p's regulatory role. The identified genes, VANGL2, BRCC3, ANP32E, and ANLN, offer insights into TNBC pathogenesis and potential therapeutic targets, laying the foundation for understanding their clinical implications in the intricate landscape of TNBC.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 4","pages":"434-443"},"PeriodicalIF":2.1000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11831748/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Iranian Journal of Basic Medical Sciences","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.22038/ijbms.2025.79808.17287","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
Objectives: Triple-negative breast cancer (TNBC), which affects 15-20% of cases, lacks targeted therapies and poses challenges in treatment. MicroRNAs (miRNAs) are potential biomarkers and therapeutic targets in breast cancer. To unravel its unique regulatory role, this study focused on miRNA microarray analysis, particularly miR-548F-3p, in TNBC samples.
Materials and methods: Using the GSE76275 dataset, gene expression profiles were analyzed using the Affymetrix Human Genome U133 Plus 2.0 Array. Differentially expressed genes (DEGs) were identified using robust preprocessing. Weighted gene co-expression network analysis (WGCNA) explored gene modules and identified hub genes co-expressed with miR-548F-3p. Functional enrichment and protein-protein interaction (PPI) network analyses were conducted. Survival analysis was used to assess the prognostic impact of the identified genes.
Results: The study found 224 up-regulated DEGs, with miR-548F-3p exhibiting significant down-regulation. MultimiR identified 400 genes that were targeted by miR-548F-3p. WGCNA revealed a blue co-expression module, with 356 genes targeted by miR-548F-3p. A Venn diagram identified common genes, including VANGL2, BRCC3, ANP32E, and ANLN. Functional enrichment highlighted crucial pathways in TNBC pathogenesis, including mitotic spindle organization, spindle assembly checkpoint signaling, cell cycle, and amino acid (serine) metabolism. PPI network analysis identified hub genes, including FOXM1, KIF23, and CDC20. VANGL2, BRCC3, ANP32E, and ANLN were significantly associated with patient outcomes in survival analysis.
Conclusion: This analysis highlighted TNBC's molecular landscape, emphasizing miR-548F-3p's regulatory role. The identified genes, VANGL2, BRCC3, ANP32E, and ANLN, offer insights into TNBC pathogenesis and potential therapeutic targets, laying the foundation for understanding their clinical implications in the intricate landscape of TNBC.
目的:三阴性乳腺癌(TNBC)影响15-20%的病例,缺乏靶向治疗,给治疗带来挑战。MicroRNAs (miRNAs)是乳腺癌潜在的生物标志物和治疗靶点。为了揭示其独特的调控作用,本研究将重点放在TNBC样本中的miRNA微阵列分析上,特别是miR-548F-3p。材料和方法:使用Affymetrix Human Genome U133 Plus 2.0 Array对GSE76275数据集的基因表达谱进行分析。差异表达基因(DEGs)通过稳健的预处理进行鉴定。加权基因共表达网络分析(WGCNA)探索基因模块,鉴定出与miR-548F-3p共表达的枢纽基因。功能富集和蛋白相互作用(PPI)网络分析。生存分析用于评估鉴定基因对预后的影响。结果:研究发现224个DEGs上调,miR-548F-3p明显下调。MultimiR鉴定出miR-548F-3p靶向的400个基因。WGCNA显示了一个蓝色共表达模块,miR-548F-3p靶向356个基因。维恩图确定了共同的基因,包括VANGL2、BRCC3、ANP32E和ANLN。功能富集强调了TNBC发病机制中的关键途径,包括有丝分裂纺锤体组织、纺锤体组装检查点信号、细胞周期和氨基酸(丝氨酸)代谢。PPI网络分析确定了枢纽基因,包括FOXM1、KIF23和CDC20。在生存分析中,VANGL2、BRCC3、ANP32E和ANLN与患者预后显著相关。结论:该分析突出了TNBC的分子格局,强调了miR-548F-3p的调控作用。这些鉴定出的基因,包括VANGL2、BRCC3、ANP32E和ANLN,为TNBC的发病机制和潜在的治疗靶点提供了新的见解,为了解它们在TNBC复杂的临床意义奠定了基础。
期刊介绍:
The Iranian Journal of Basic Medical Sciences (IJBMS) is a peer-reviewed, monthly publication by Mashhad University of Medical Sciences (MUMS), Mashhad, Iran . The Journal of "IJBMS” is a modern forum for scientific communication. Data and information, useful to investigators in any discipline in basic medical sciences mainly including Anatomical Sciences, Biochemistry, Genetics, Immunology, Microbiology, Pathology, Pharmacology, Pharmaceutical Sciences, and Physiology, will be published after they have been peer reviewed. This will also include reviews and multidisciplinary research.