Identification of shared hub genes CTNNB1, TJP1, PTK2, and TP53 associated with endothelial proliferation in infantile hemangioma and glioblastoma.

Abstract

Infantile hemangioma (IH) and glioblastoma multiforme (GBM) are clinically distinct but share vascular and proliferative characteristics. This study aimed to identify common transcriptional and regulatory mechanisms between IH and GBM to uncover potential hub genes driving disease progression. Transcriptomic datasets GSE127487 (IH) and GSE108476 (GBM) were analyzed using the limma package in R. Differentially expressed genes (DEGs) were overlapped to identify shared signatures. Protein-protein interaction networks were built using STRING and analyzed in Cytoscape to determine hub genes via CytoHubba. Gene expression, promoter methylation, mutation, and CNV data were validated using OncoDB, GEO2R, UALCAN, and cBioPortal. Functional enrichment and drug sensitivity analyses were performed using DAVID and GSCA. Experimental validation included siRNA knockdown or overexpression of target genes in HemSCs, HemECs, U87-MG, and LN229 cells, followed by RT-qPCR, western blot, proliferation, colony formation, and wound-healing assays. A total of 142 common DEGs were identified, with four hub genes, including TP53, CTNNB1, TJP1, and PTK2 showing consistent dysregulation. TP53 and CTNNB1 were upregulated, while TJP1 and PTK2 were downregulated in both IH and GBM. Methylation, mutation, and CNV analyses supported their regulatory involvement. Functional assays confirmed that CTNNB1 knockdown and TJP1/PTK2 overexpression suppressed proliferation and migration. This integrative study identifies CTNNB1, TJP1, PTK2, and TP53 as shared hub genes, highlighting common molecular regulators of endothelial proliferation and tumor-associated phenotypes in IH and GBM, and suggesting potential therapeutic targets.