microRNA-4500 inhibits human glioma cell progression by targeting IGF2BP1.

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. ● miR-4500 targets IGF2BP1 in human glioma cells ● Ectopic overexpression of miR-4500 inhibits IGF2BP1 expression and glioma cell progression ● miR-4500 inhibition increases IGF2BP1 expression and promotes glioma cell progression ● IGF2BP1 knockout mimics and abolishes miR-4500-induced actions in glioma cells ● miR-4500 downregulation in human glioma tissues correlates with IGF2BP1 upregulation [ABSTRACT FROM AUTHOR]