Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Sci Rep. 2017 Sep 19;7(1):11846. doi: 10.1038/s41598-017-10674-7.
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.
婴儿血管瘤是婴儿中最常见的良性肿瘤。许多研究证实，碱性成纤维细胞生长因子(bFGF)及其关键受体 FGFR1 在血管瘤中高度表达。此外，几种 miRNAs 可以调节血管生成。在这方面，miR-424 通常作为肿瘤抑制基因发挥作用。本研究旨在探讨 miR-424 在婴儿皮肤血管瘤中的作用机制。我们的结果表明，miR-424 在婴儿皮肤血管瘤组织中表达较低，miR-424 过表达下调血管瘤衍生内皮细胞中 FGFR1 的表达，而 miR-424 抑制则上调 FGFR1 的表达。荧光素酶报告基因分析证实 FGFR1 是 miR-424 的靶基因。CCK-8、流式细胞术、Transwell 迁移和管形成实验表明，miR-424 过表达至少部分通过阻断 bFGF/FGFR1 通路抑制细胞增殖、迁移和管形成。相比之下，miR-424 抑制显著增强了这些功能。此外，miR-424 过表达显著抑制 ERK1/2 磷酸化，而 miR-424 抑制增强 ERK1/2 磷酸化。总之，miR-424 可以抑制 bFGF/FGFR1 通路，从而抑制 ERK1/2 磷酸化，进而抑制细胞增殖、迁移和管形成能力以及婴儿皮肤血管瘤的发展。
