胰岛素样生长因子II mRNA结合蛋白3促进人胶质母细胞瘤细胞的增殖、迁移和侵袭。

Insulin-like growth factor II mRNA-binding protein 3 promotes cell proliferation, migration and invasion in human glioblastoma.

作者信息

Wu Chao, Ma Hongxin, Qi Guijun, Chen Fanyu, Chu Jiancheng

机构信息

Department of Neurosurgery, Tengzhou Central People's Hospital, Tengzhou, Shandong 277500, People's Republic of China.

出版信息

Onco Targets Ther. 2019 May 15;12:3661-3670. doi: 10.2147/OTT.S200901. eCollection 2019.

Abstract

Recently, the insulin-like growth factor mRNA-binding protein 3 (IMP3) has been reported to be involved in tumorigenesis. We aimed to study the expression and role of IMP3 in human glioblastoma. We analyzed the expression of IMP3 in 70 cases of glioma tissues, normal brain tissues and 5 kinds of cell lines using western blot. Immunohistochemistry (IHC) was used to evaluate the expression and distribution of IMP3 in glioma tissues. Colony formation, wound healing, migration and invasion assays and tumorigenesis in nude mice were used to explore the function of IMP3 in vitro and in vivo. The epithelial-mesenchymal transition (EMT)-related biomarkers were detected by western blot. We found that the expression level of IMP3 was obviously higher in glioma tissues than that in normal brain tissues, and associated with glioma grade. In-vitro assays revealed that IMP3 overexpression significantly induced cell proliferation, migration, and invasion. Mechanically, IMP3 over-expression downregulated the expression of E-cadherin, but upregulated the expressions of N-cadherin, vimentin, snail, slug and MMP9. However, the inhibition of IMP3 impaired these oncogenic effects. In vivo assay also demonstrated that silencing of IMP3 inhibited tumor growth and improved survival of tumor-bearing xenograft nude mice. IMP3 can promote cell proliferation, migration and invasion by inducing EMT in glioblastoma. Thus, targeting IMP3 pathway may be a novel way to treat patients with glioblastoma.

摘要

最近,有报道称胰岛素样生长因子mRNA结合蛋白3(IMP3)参与肿瘤发生。我们旨在研究IMP3在人胶质母细胞瘤中的表达及作用。我们采用蛋白质免疫印迹法分析了70例胶质瘤组织、正常脑组织及5种细胞系中IMP3的表达。免疫组织化学(IHC)用于评估IMP3在胶质瘤组织中的表达及分布。采用集落形成、伤口愈合、迁移和侵袭实验以及裸鼠成瘤实验来探究IMP3在体外和体内的功能。通过蛋白质免疫印迹法检测上皮-间质转化(EMT)相关生物标志物。我们发现,IMP3在胶质瘤组织中的表达水平明显高于正常脑组织,且与胶质瘤分级相关。体外实验表明,IMP3过表达显著诱导细胞增殖、迁移和侵袭。机制上,IMP3过表达下调E-钙黏蛋白的表达,但上调N-钙黏蛋白、波形蛋白、蜗牛蛋白、蛞蝓蛋白和基质金属蛋白酶9的表达。然而,抑制IMP3可削弱这些致癌作用。体内实验也表明,沉默IMP3可抑制肿瘤生长并提高荷瘤异种移植裸鼠的生存率。IMP3可通过诱导胶质母细胞瘤中的EMT促进细胞增殖、迁移和侵袭。因此,靶向IMP3通路可能是治疗胶质母细胞瘤患者的一种新方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2730/6527097/c92b69dd4494/OTT-12-3661-g0001.jpg

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