Neurosurgery Department, Xuzhou Children's Hospital, Xuzhou Medical University, Xuzhou, China.
Department of Ultrasound, The Second Affiliated Hospital of Soochow University, Suzhou, China.
Biochem Biophys Res Commun. 2019 Jun 11;513(4):800-806. doi: 10.1016/j.bbrc.2019.04.058. Epub 2019 Apr 16.
Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) overexpression promotes glioma cell progression. The aim of the current study is to silence IGF2BP1 in glioma cells by the microRNA (miRNA) strategy. The bio-informatic analyses identified that microRNA-4500 (miR-4500) putatively targets 3'-UTR (3'-untranslated region) of IGF2BP1. In A172 cells and primary human glioma cells ectopic overexpression of the wild-type miR-4500 (but not the mutant form) downregulated IGF2BP1 and its target genes (Gli1, IGF2 and c-Myc). Functional studies show that ectopic miR-4500 overexpression inhibited glioma cell growth, survival, proliferation, migration and invasion. Conversely, in A172 cells miR-4500 inhibition, by a lentiviral construct, increased expression of IGF2BP1 and its targets, promoting cell survival, proliferation and migration. Furthermore, IGF2BP1 knockout by the CRISPR/Cas9 method inhibited A172 cell progression. Significantly, miR-4500 overexpression or miR-4500 inhibition was ineffective in IGF2BP1 knockout A172 cells. At last, we show that miR-4500 levels are downregulated in human glioma tissues, correlating with IGF2BP1 upregulation. Together, we conclude that miR-4500 inhibits human glioma cell progression by targeting IGF2BP1.
胰岛素样生长因子 2 mRNA 结合蛋白 1（IGF2BP1）过表达促进神经胶质瘤细胞的进展。本研究的目的是通过 microRNA（miRNA）策略沉默神经胶质瘤细胞中的 IGF2BP1。生物信息学分析表明 microRNA-4500（miR-4500）可能靶向 IGF2BP1 的 3'UTR（3'非翻译区）。在 A172 细胞和原代人神经胶质瘤细胞中，外源性过表达野生型 miR-4500（而非突变型）下调 IGF2BP1 及其靶基因（Gli1、IGF2 和 c-Myc）。功能研究表明，外源性 miR-4500 过表达抑制神经胶质瘤细胞的生长、存活、增殖、迁移和侵袭。相反，在 A172 细胞中，通过慢病毒构建体抑制 miR-4500 表达增加了 IGF2BP1 及其靶基因的表达，促进了细胞的存活、增殖和迁移。此外，通过 CRISPR/Cas9 方法敲除 IGF2BP1 抑制了 A172 细胞的进展。重要的是，在 IGF2BP1 敲除的 A172 细胞中，miR-4500 的过表达或抑制均无效。最后，我们表明 miR-4500 在人神经胶质瘤组织中表达下调，与 IGF2BP1 的上调相关。综上所述，miR-4500 通过靶向 IGF2BP1 抑制人神经胶质瘤细胞的进展。
