Bone Marrow Mesenchymal Stem Cells (BMSC)-Originated miR-133 Impedes Migration and Invasiveness of Glioma Cells While Enhancing Apoptosis via Targeting the Receptor for Activated C Kinase 1 (RACK1)

Abstract

This study aims to dissect the effects of bone marrow mesenchymal stem cells (BMSC) on the in vitro activity of glioma cells and the underlying mechanisms. The glioma cells were transfected with miR-133 mimics, RACK1-Vector, negative control (NC) and miR-133 mimic+RACK1-Vector, respectively, and then co-cultured with BMSC followed by analysis of miR-133 expression via PCR, apoptosis via flow cytometry, proliferation via CCK-8, invasion and migration via Transwell assay, the expression of proteins involved in apoptosis, anti-apoptosis, invasiveness and RACK1 by western blot, and the targeting relationship between miR-133 and RACK1 by dual-luciferase reporter gene assay. In comparison with normal glial cells, glioma cells exhibited a significantly diminished miR-133 level. miR-133 was upregulated in glioma cells after co-culture with BMSC, along with significantly restrained proliferation rate, migration and invasion activities as well as reduced protein levels (MMP-2, Vimentin, N-cadherin and MMP-9). Mechanistic study showed that miR-133 can retard the expression of RACK1, thereby impeding the invasion, migration and proliferation activities of cells while triggering cell apoptosis. In conclusion, BMSC-originated miR-133 can impede the migration and invasion while enhancing the apoptosis of glioma cells via targeting RACK1.