Dynamic alterations in m⁶A RNA methylation profiles during involution of infantile hemangiomas

Infantile hemangioma (IH) is a common benign vascular tumor characterized by a proliferative phase followed by regression. N6-methyladenosine (m6A) methylation, a major RNA modification, plays a critical role in tumor development, though its function in IH remains unclear.

This study analyzed six IH samples (three from proliferative IH, three from involuting IH), using transcript-specific microarrays after m6A immunoprecipitation to explore dynamic methylation changes and their regulatory impact on gene expression.

Results showed significantly lower m6A levels in involuting-phase hemangiomas. Differentially methylated genes (DMGs) were mainly involved in biological processes such as cell-cell junction and cell-matrix adhesion. KEGG pathway analysis revealed DMGs were enriched in MAPK, Calcium, and PI3K-Akt signaling pathways, suggesting that m6A modifications are closely linked to angiogenesis and tumor growth. MeRIP-qPCR showed that IGF1 and IGF2 exhibiting significant correlation in both m6A levels and expression. The overall downregulation of m6A modification for lncRNA and sncRNA suggested active demethylation processes may involve in involution of IH.

Overall, this study demonstrates that m6A methylation modulates key cellular pathways in IH progression and may serve as a promising target for future diagnostic and therapeutic strategies.