von Willebrand factor rescued by miR-24 inhibition facilitates the proliferation and migration of osteosarcoma cells in vitro
von Willebrand factor rescued by miR-24 inhibition facilitates the proliferation and migration of osteosarcoma cells in vitro
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抑制miR-24拯救冯维勒布兰德因子促进骨肉瘤细胞体外增殖和迁移
DOI：
10.1042/bsr20180372
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发表时间：
2018-12-21
影响因子：
4
通讯作者：
Ling, Jing
中科院分区：
文献类型：
--
作者：
Liu, Ling;Pan, Jun;Ling, Jing
血管性血友病因子（vWF）是一种主要的促凝血分子，其显示出在转移性和原发性骨肉瘤（OS）组织之间的区别，并且与增加的转移有关。然而，其在OS进展中的功能作用尚不清楚。采用免疫荧光标记和实时荧光定量PCR技术分析vWF和miR-24在人OS组织中的表达谱。通过双荧光素酶报告基因分析鉴定miR-24与vWF之间的相互作用。通过细胞增殖、集落形成和迁移评估vWF和miR-24对OS细胞的影响。使用Kaplan-Meier分析和Pearson卡方检验分析OS患者中miR-24的临床意义。在此，我们报道了OS组织中vWF的表达显著增加，但miR-24的表达显著降低（n=84）。在MG-63和U2 OS细胞中，vWF被进一步验证为miR-24的靶标。miR-24明显抑制MG-63和U2 OS细胞的增殖和迁移。然而，miR-24的迁移抑制活性主要通过vWF过表达减弱。临床上，人OS组织中miR-24的低表达与肿瘤转移显著相关，并预测OS患者的生存率较差。本研究表明vWF作为miR-24的下游效应子在控制OS细胞进展中发挥重要作用。因此，靶向miR-24或vWF有望成为OS治疗的有效生物学靶标。
von Willebrand factor (vWF) is a major procoagulant molecule that was shown to differentiate between metastatic and primary osteosarcoma (OS) tissues and associated with increased metastasis. However, its functional role in OS progression has been unclear yet. The expression profile of vWF and miR-24 in human OS tissues was characterized using immunofluorescence labeling and quantitative real-time PCR analysis. The interaction between miR-24 and vWF was identified by dual luciferase reporter assay. The effects of vWF and miR-24 on OS cells were assessed by cell proliferation, colony formation, and migration. The clinical significance of miR-24 in OS patients was analyzed using Kaplan–Meier analyses and Pearson’s Chi-squared test. Here, we reported that the expression of vWF was significantly increased, but miR-24 was significantly decreased in OS tissues (n=84). vWF was further validated as the target of miR-24 in MG-63 and U2OS cells. miR-24 obviously suppressed the proliferation and migration of MG-63 and U2OS cells. However, the migration-inhibiting activity of miR-24 was predominantly attenuated by vWF overexpression. Clinically, low miR-24 expression in human OS tissues was significantly associated with tumor metastasis and predicted a poor survival in OS patients. This work demonstrated that vWF, as a downstream effector of miR-24, played an important role in controlling OS cell progression. Target miR-24 or vWF, therefore, promises to be an effective biological target for OS treatment.