miR-429 Suppresses Proliferation and Migration in Glioblastoma Cells and Induces Cell-cycle Arrest via Modulating Several Target Genes of ERBB Signaling Pathway

Abstract

Glioblastoma is aggressive and lethal brain cancer, which is incurable by cancer standard treatments. miRNAs have great potential to be used for gene therapy due to their ability to modulate several target genes simultaneously. We found miR-429 is downregulated in glioblastoma and has several predicted target genes from the ERBB signaling pathway using bioinformatics tools. ERBB is the most over-activated genetic pathway in glioblastoma patients, which is responsible for augmented cell proliferation and migration in glioblastoma multiforme (GBM). Here we overexpressed miR-429 using lentiviral vectors in GBM U-251 cells and observed that the expression level of several oncogenes of the ERBB pathway, EGFR, PIK3CA, PIK3CB, KRAS, and MYC significantly decreased; as shown by real-time PCR and western blotting. Using the luciferase assay, we showed that miR-429 directly targets MYC, BCL2, and EGFR. In comparison to scrambled control, miR-429 had a significant inhibitory effect on cell proliferation and migration as deduced from MTT and scratch wound assays and induced cell-cycle arrest in flow cytometry. Altogether miR-429 seems to be an efficient suppressor of the ERBB genetic signaling pathway and a potential therapeutic for glioblastoma.