Wu Pinru, Cen Qingqing, Shang Ying, Liang Junyan, Ma Gang
Department of Laser and Aesthetic Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Dermatology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Oncol. 2025 Sep 4;15:1652621. doi: 10.3389/fonc.2025.1652621. eCollection 2025.
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.
婴儿血管瘤(IH)是一种常见的良性血管肿瘤,其特征是经历增殖期后进入消退期。N6-甲基腺苷(m6A)甲基化是一种主要的RNA修饰,在肿瘤发展中起关键作用,但其在婴儿血管瘤中的功能尚不清楚。
本研究分析了6个婴儿血管瘤样本(3个来自增殖期婴儿血管瘤,3个来自消退期婴儿血管瘤),在进行m6A免疫沉淀后使用转录本特异性微阵列来探索动态甲基化变化及其对基因表达的调控影响。
结果显示消退期血管瘤中的m6A水平显著降低。差异甲基化基因(DMG)主要参与细胞间连接和细胞-基质黏附等生物学过程。KEGG通路分析显示DMG在MAPK、钙和PI3K-Akt信号通路中富集,表明m6A修饰与血管生成和肿瘤生长密切相关。MeRIP-qPCR显示IGF1和IGF2在m6A水平和表达上均表现出显著相关性。lncRNA和sncRNA的m6A修饰总体下调表明活跃的去甲基化过程可能参与婴儿血管瘤的消退。
总体而言,本研究表明m6A甲基化在婴儿血管瘤进展过程中调节关键细胞通路,可能成为未来诊断和治疗策略的一个有前景的靶点。