婴儿血管瘤（IH）是由血管生成和血管形成失调引起的。被去泛素化酶OTUB1（OTU结构域，泛素醛结合1）报道在多种癌症中发挥了重要作用；然而，其在IH进展和调节血管生成的潜在机制仍不清楚。使用Transwell实验、EdU实验和管形成实验来研究IH在体外的生物学行为。建立IH动物模型来评估IH在体内的进展。进行质谱分析以检测OTUB1的下游和转化生长因子beta诱导(TGFBI)的泛素化位点。进行半衰测试和泛素化测试来研究TGFBI与OTUB1之间的相互作用。通过胞外酸化率实验来评估IH的糖酵解水平。与逆转和逆转IH组织比较，OTUB1的表达在增殖IH中明显增加。通过体外实验，OTUB1的沉默抑制了人血管瘤内皮细胞的增殖、迁移和管形成，而OTUB1的过表达促进了人血管瘤内皮细胞的增殖、迁移和血管生成能力。OTUB1的沉默显著抑制了IH在体内的进展。此外，通过质谱分析，预测TGFBI是IH中OTUB1的功能性下游靶标。在机械上，OTUB1与TGFBI在K22和K25残基上相互作用并脱泛素化，这与OTUB1的催化活性无关。OTUB1沉默对人血管瘤内皮细胞的细胞增殖、迁移和管形成能力的抑制作用被TGFBI过表达逆转。此外，我们发现OTUB1通过调节TGFBI介导糖酵解作用，从而促进婴儿血管瘤的血管生成。OTUB1以一种非催化的方式脱泛素化TGFBI，并通过调节糖酵解作用促进婴儿血管瘤的血管生成。靶向OTUB1可能是抑制IH进展和肿瘤的有效治疗策略。

Infantile hemangioma (IH) arises as a result of dysregulation of both angiogenesis and vasculogenesis. The deubiquitylase OTUB1 (OTU domain, ubiquitin aldehyde binding 1) has been reported to play an essential role in multiple cancers; however, its function in the progression of IH and the underlying mechanisms regulating angiogenesis remain unclear.Transwell assays, EdU assays, and tube formation assays were performed to investigate the biological behavior of IH in vitro. IH animal models were established to estimate the progression of IH in vivo. Mass spectrometric analysis were conducted to detect the downstream of OTUB1 and ubiquitination sites of transforming growth factor beta induced (TGFBI). Half-life assays and ubiquitination test were performed to investigate the interaction between TGFBI and OTUB1. Extracellular acidification rate assays were employed to estimate the glycolysis level in IH.The expression of OTUB1 was obviously increased in proliferating IH as compared to the involuting and involuted IH tissues. Through in vitro experiments, the knockdown of OTUB1 inhibited the proliferation, migration and tube formation of human hemangioma endothelial cells, while the overexpression of OTUB1 promoted the proliferation, migration and angiogenic abilities of human hemangioma endothelial cells. The knockdown of OTUB1 significantly suppressed IH progression in vivo. Furthermore, TGFBI was predicted as a functional downstream target of OTUB1 in IH by mass spectrometry. Mechanistically, OTUB1 interacted with and deubiquitylated TGFBI on the K22 and K25 residues, which was demonstrated to be independent of the catalytic activity of OTUB1. The inhibitory effects of OTUB1 knockdown on cell proliferation, migration and tube formation ability of human hemangioma endothelial cells were reversed by TGFBI overexpression. Further, we found that OTUB1 mediated glycolysis by regulating TGFBI in infantile hemangioma.OTUB1 deubiquitinates TGFBI in a catalytic-independent manner and promotes angiogenesis in infantile hemangiomas by regulating glycolysis. Targeting OTUB1 might be an effective therapeutic strategy for inhibiting IH progression and tumor.