Targeting ESM1 via SOX4 promotes the progression of infantile hemangioma through the PI3K/AKT signaling pathway

Background: Infantile hemangioma (IH) is the most prevalent benign vascular tumor in children, yet its pathogenesis remains incompletely understood. Research has established a strong association between SOX4 and tumor blood vessel formation. The objective of this study was to investigate the function and underlying mechanism of SOX4 in IH development with the aim of identifying novel therapeutic targets.

Methods: We identified the transcription factor SOX4 associated with IH through RNA-seq screening of IH microtumors and validated it in IH tissues. The effect of SOX4 on the biological behavior of CD31+ hemangioma-derived endothelial cells (HemECs) was investigated via in vitro cell experiments. In addition, RNA-seq analysis was performed on CD31+ HemECs with low expression levels of SOX4, and the target genes of SOX4 were identified. Finally, the effect of SOX4 on tumor angiogenesis was further elucidated through 3D microtumor and animal experiments.

Results: SOX4 is highly expressed in IH tissues and promotes the proliferation, migration, and angiogenesis of CD31+ HemECs. In addition, SOX4 binds to the endothelial cell-specific molecule 1 (ESM1) promoter to promote the progression of the PI3K/AKT signaling pathway. Finally, through IH 3D microtumor and animal experiments, SOX4 and ESM1 are shown to be tumorigenic genes that independently promote tumor progression.

Conclusions: SOX4 plays a crucial role in the progression of IH, and the SOX4/ESM1 axis may serve as a novel biomarker and potential therapeutic target for IH.