Infantile hemangioma is the most common soft tissue tumors in childhood. In clinic, propranolol is widely used for infantile hemangioma therapy. However, some of the infantile hemangioma patients display resistance to propranolol treatment. Previous studies show that miR-187-3p is inhibited in hepatocellular carcinoma and lung cancer, while the role of miR-187-3p in infantile hemangioma remains unclear. In the present study, we explore the biological role of miR-187-3p in infantile hemangioma. The mRNA and protein levels of related genes were detected by real-time PCR and Western blotting. CCK8 assay was used to detect cell viability and IC50 values of propranolol. Cell apoptosis was detected by Caspase-3 Activity assay. Luciferase reporter assay and biotin RNA pull down assay were used to detect the interaction between miR-187-3p and the targeted gene. MiR-187-3p was down-regulated in infantile hemangioma tissues and promoted propranolol sensitivity of HemSCs. Mechanically, NIPBL was the direct target of miR-187-3p in HemSCs. NIPBL downregulation inhibited propranolol resistance of HemSCs. Re-introduction of NIPBL reversed miR-187-3p-meidated higher propranolol sensitivity of HemSCs. MiR-187-3p enhanced propranolol sensitivity of hemangioma stem cells via targeting NIPBL. MiR-187-3p may serve as a novel prognostic indicator and potential target for infantile hemangioma therapy.Key words: MiR-187-3p, infantile hemangioma, propranolol, resistance, NIPBL.

中文翻译：

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MiR-187-3p增强血管瘤干细胞对普萘洛尔的敏感性。

小儿血管瘤是儿童期最常见的软组织肿瘤。在临床上，普萘洛尔被广泛用于婴儿血管瘤治疗。但是，一些婴儿血管瘤患者对普萘洛尔治疗表现出抗药性。先前的研究表明，miR-187-3p在肝细胞癌和肺癌中受到抑制，而miR-187-3p在婴儿血管瘤中的作用尚不清楚。在本研究中，我们探讨了miR-187-3p在婴儿血管瘤中的生物学作用。通过实时PCR和Western印迹检测相关基因的mRNA和蛋白质水平。CCK8测定法用于检测普萘洛尔的细胞活力和IC50值。通过Caspase-3活性测定法检测细胞凋亡。荧光素酶报告基因测定法和生物素RNA下拉测定法用于检测miR-187-3p与靶基因之间的相互作用。MiR-187-3p在婴儿血管瘤组织中下调，并增强了HemSCs的普萘洛尔敏感性。从机械上讲，NIPBL是HemSCs中miR-187-3p的直接靶标。NIPBL下调抑制了HemSCs对心得安的抗药性。重新引入NIPBL可以逆转miR-187-3p介导的对HemSCs更高的普萘洛尔敏感性。MiR-187-3p通过靶向NIPBL增强血管瘤干细胞对心得安的敏感性。关键词：MiR-187-3p，可作为婴儿血管瘤治疗的新的预后指标和潜在靶标。关键词：MiR-187-3p，婴儿血管瘤，普萘洛尔，耐药，NIPBL MiR-187-3p在婴儿血管瘤组织中下调，并增强了HemSCs的普萘洛尔敏感性。从机械上讲，NIPBL是HemSCs中miR-187-3p的直接靶标。NIPBL下调抑制了HemSCs对心得安的抗药性。重新引入NIPBL可以逆转miR-187-3p介导的对HemSCs更高的普萘洛尔敏感性。MiR-187-3p通过靶向NIPBL增强血管瘤干细胞对心得安的敏感性。关键词：MiR-187-3p，可作为婴儿血管瘤治疗的新的预后指标和潜在靶标。关键词：MiR-187-3p，婴儿血管瘤，普萘洛尔，耐药，NIPBL MiR-187-3p在婴儿血管瘤组织中下调，并增强了HemSCs的普萘洛尔敏感性。从机械上讲，NIPBL是HemSCs中miR-187-3p的直接靶标。NIPBL下调抑制了HemSCs对心得安的抗药性。重新引入NIPBL可以逆转miR-187-3p介导的HemSCs对普萘洛尔的更高敏感性。MiR-187-3p通过靶向NIPBL增强血管瘤干细胞对心得安的敏感性。关键词：MiR-187-3p，可作为婴儿血管瘤治疗的新的预后指标和潜在靶标。关键词：MiR-187-3p，婴儿血管瘤，普萘洛尔，耐药，NIPBL MiR-187-3p通过靶向NIPBL增强血管瘤干细胞对心得安的敏感性。关键词：MiR-187-3p，可作为婴儿血管瘤治疗的新的预后指标和潜在靶标。关键词：MiR-187-3p，婴儿血管瘤，普萘洛尔，耐药，NIPBL MiR-187-3p通过靶向NIPBL增强血管瘤干细胞对心得安的敏感性。关键词：MiR-187-3p，可作为婴儿血管瘤治疗的新的预后指标和潜在靶标。关键词：MiR-187-3p，婴儿血管瘤，普萘洛尔，耐药，NIPBL