Table 1. Potential therapeutic targets/drugs.

Literature	Research methods	Target/drug	Mechanisms
Zhang et al. (129)	In vivo, in vitro	Macrophages	Macrophages in IHs promoted the progression of hemangioma by promoting lesion proliferation and endothelial cell differentiation while inhibiting lipogenesis of hemangioma stem cells, thereby promoting the progression of hemangioma
Wu et al. (130)	In vitro	M1 macrophages	M1 macrophage induced the transformation of endothelial cells in hemangioma into mesenchyme, promoting hemangioma regression
Li et al. (131)	In vitro, immunohistochemistry, quantitative RT-PCR	PEDF	PEDF expression was increased during the IH regression phase and may have effects on promoting IH regression
Itinteang et al. (132)	In vitro, immunohistochemistry, enzyme activity assays, mass spectrometry, and Nano String gene expression assay	Cathepsins B, D, G	The expression of cathepsins B, D, and G was detected in various stages of IHs. Cathepsin B promoted the production of renin; cathepsin D induced the production of angiotensin I, and cathepsin G induced the conversion of angiotensin I to angiotensin II (Figure 1)
Chisholm et al. (133); Dal et al. (134)	In vitro, histochemistry, immunohistochemistry, enzyme-linked immunosorbent assay, and colorimetry	β3-adrenergic receptor	the β3-adrenergic receptor was highly expressed in various stages of IHs and played a role in the pathogenesis of IHs, stimulating the release of VEGF and affecting various intracellular pathways and vascular functions
Amaya et al. (135)	In vitro, histochemistry, and immunohistochemistry	Programmed cell death protein-1 (PD-1)	Programmed cell death protein 1 was highly expressed in endothelial cells, whereas expression of programmed death-ligand 1 was negative in six IH cases, which provided the possibility for immunotherapy
Cai et al. (136)	In vivo, in vitro	15,16-dihydrotanshinone I	Increased expression of apoptosis-associated proteins and significantly inhibited angiogenesis. In vivo experiments showed significant inhibition of hemangiomas
Wang et al. (137); Liu et al. (138)	In vitro, histochemistry	Linc00152	Linc00152 was highly expressed in IH tissues. Downregulation of Linc00152 expression inhibited Akt/mTOR and Notch1 pathways, thereby inhibiting the proliferation of endothelial cells and inducing apoptosis in the hemangiomas
Zhang et al. (139)	In vitro, histochemistry	UCA1	UCA1 was upregulated during the proliferative phase of hemangiomas. Inhibition of UCA1 expression upregulated miR-200c expression subsequently and further inhibited mTOR, AMPK, and Wnt/β-catenin pathways, thereby inhibiting cell proliferation, migration, and invasion of hemangiomas.

PEDF, pigment epithelium-derived factor; Linc00152, a long non-coding RNA; UCA1, urothelial carcinoma associated 1.