Abstract
Infantile hemangioma is the most common benign tumor in infants. Many studies have confirmed that basic fibroblast growth factor (bFGF) and its key receptor FGFR1 are highly expressed in hemangioma. Moreover, several miRNAs can regulate angiogenesis. In this regard, miR-424 often plays a role as tumor suppressor gene. This study was designed to investigate the mechanism of miR-424 in infantile skin hemangioma. Our results showed low expression of miR-424 in infantile skin hemangioma tissues, and that miR-424 overexpression downregulated FGFR1 expression in hemangioma-derived endothelial cells, while miR-424 inhibition upregulated FGFR1 expression. Luciferase reporter analysis confirmed that FGFR1 was a target gene of miR-424. CCK-8, flow cytometry, transwell migration and tube formation assays demonstrated that miR-424 overexpression inhibited cell proliferation, migration and tube formation, at least in part by blocking the bFGF/FGFR1 pathway. In contrast, miR-424 inhibition significantly enhanced these functions. Furthermore, miR-424 overexpression significantly inhibited ERK1/2 phosphorylation, whereas miR-424 inhibition enhanced ERK1/2 phosphorylation. In conclusion, miR-424 could suppress the bFGF/FGFR1 pathway, thereby inhibit ERK1/2 phosphorylation, and thus inhibit cell proliferation, migration and tube formation capabilities and the development of infantile skin hemangioma.
Highlights
Infantile hemangioma (IH) is the most common benign vascular lesion in infants and young children, and it is characterized by the abnormal growth of endothelial cells
Our study indicated that miR-424 may reduce fibroblast growth factor receptor 1 (FGFR1) expression, suppress the basic fibroblast growth factor (bFGF)/FGFR1 pathway, thereby inhibit Extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation, and inhibit the cell proliferation, migration and tube formation capabilities and the development of infantile skin hemangioma
Many studies have reported that bFGF and its receptor FGFR1 are highly expressed in hemangiomas
Summary
Infantile hemangioma (IH) is the most common benign vascular lesion in infants and young children, and it is characterized by the abnormal growth of endothelial cells. These lesions can grow invasively and/or be located on relatively important tissues, and approximately ten percent of hemangiomas grow quickly In these cases, the tumors can cause many problems and even disrupt normal tissue or threaten the life of the patient[9,10]. MicroRNAs (miRNAs) are a class of non-coding, small-molecule, single-stranded RNAs (generally 18 to 22 nucleotides in length) that are highly evolutionarily conserved They are involved in the regulation of various pathophysiological processes, such as cell proliferation, differentiation and apoptosis. Our aim was to investigate the expression, role and mechanism of miR-424 in infantile skin hemangioma. Our study indicated that miR-424 may reduce FGFR1 expression, suppress the bFGF/FGFR1 pathway, thereby inhibit ERK1/2 phosphorylation, and inhibit the cell proliferation, migration and tube formation capabilities and the development of infantile skin hemangioma
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