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Abstract
Objective To explore the potential molecular dysregulation mechanism of infantile hemangioma (IH) through analysis of gene expression datasets and in vitro experiments. Methods Gene expression data of IH growth and regression phases, as well as hemangioma endothelial cell (HemEC) and hemangioma stem cell, were obtained from GSE127487 and GSE216867 in Gene Expression Omnibus (GEO) datasets. Differentially expressed analysis, protein-protein interaction (PPI) network analysis, and enrichment analysis were performed to screen hub genes and key signaling pathways. Using simple random
sampling, a total of 10 IH children admitted to Xinjiang Uygur Autonomous Region Children's Hospital from
December 2023 to June 2024 were selected as the IH group, and another 10 healthy children were selected as the control group. Serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay (ELISA). The expression of hub genes and related signaling pathway proteins was detected by Western blotting. Fibronectin 1 (FN1) was knocked down in HemEC, and cells were divided into three groups: HemEC group, HemEC+si-NC group, and HemEC+si-FN1 group. Cell migration and invasion were evaluated by Transwell assay, and apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Statistical analysis was performed using t-test, one-way analysis of variance. Results A total of 2 226 differentially expressed gene (DEG) were identified in GSE127487 and 164 DEG in GSE216867, with 49 overlapping DEG between the two datasets. PPI network analysis showed that FN1 had the highest connectivity and was identified as the hub gene. Enrichment analysis revealed that FN1 was significantly enriched in the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) and Ras-related protein 1 (Rap1) signaling pathways. Compared with control group, IH group exhibited significantly higher expression levels of IL-6, TNF-α, FN1, phosphorylated PI3K (p-PI3K), phosphorylated Akt (p-Akt), Rap1, and cell division cycle 42 (CDC42) (all P<0.001). Knockdown of FN1 in HemEC markedly reduced the expression of FN1, p-PI3K, p-Akt, Rap1, and CDC42, suppressed cell migration and invasion, and promoted cell apoptosis (all P<0.001). Conclusion FN1 may play a critical role in the progression of IH by regulating the PI3K/Akt and Rap1 signaling pathways.
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2026, Vol. 14 
