The expression of EMX2 lead to cell cycle arrest in glioblastoma cell line

Annabelle Monnier,Jean Mosser,Régis Bouvet,Marc Aubry,Amandine Etcheverry,Rachel Boniface,Véronique Quillien,Tony Avril,Eric Chevet

doi:10.1186/s12885-018-5094-y

Abstract

BackgroundGlioblastoma (GB) is a highly invasive primary brain tumor that nearly always systematically recurs at the site of resection despite aggressive radio-chemotherapy. Previously, we reported a gene expression signature related to tumor infiltration. Within this signature, the EMX2 gene encodes a homeodomain transcription factor that we found was down regulated in glioblastoma. As EMX2 is reported to play a role in carcinogenesis, we investigated the impact of EMX2 overexpression in glioma-related cell lines.MethodsFor that purpose, we constructed tetracycline-inducible EMX2 expression lines. Transfected cell phenotypes (proliferation, cell death and cell cycle) were assessed in time-course experiments.ResultsRestoration of EMX2 expression in U87 glioblastoma cells significantly inhibited cell proliferation. This inhibition was reversible after EMX2 removal from cells. EMX2-induced proliferative inhibition was very likely due to cell cycle arrest in G1/S transition and was not accompanied by signs of cell death.ConclusionOur results suggest that EMX2 may constitute a putative therapeutic target for GB treatment.Further studies are required to decipher the gene networks and transduction signals involved in EMX2’s effect on cell proliferation.

Highlights

Glioblastoma (GB) is a highly invasive primary brain tumor that nearly always systematically recurs at the site of resection despite aggressive radio-chemotherapy
Empty Spiracles Homeobox 2 (EMX2) expression is low in GB and GB cell lines To assess EMX2 mRNA expression level, we focused on a previously reported transcriptome gene signature associated with GB intratumor heterogeneity
[10] We observed a significant decrease of EMX2 expression in GB tumor and necrotic zones compared to paired interface and peripheral brain zones derived from the same patients (n = 10) (Fig. 2a)

Summary

Introduction

Glioblastoma (GB) is a highly invasive primary brain tumor that nearly always systematically recurs at the site of resection despite aggressive radio-chemotherapy. We reported a gene expression signature related to tumor infiltration Within this signature, the EMX2 gene encodes a homeodomain transcription factor that we found was down regulated in glioblastoma. GB has been extensively characterized at the genomic, transcriptomic and epigenomic levels and is described as a molecularly heterogeneous disease at both inter- and intratumor levels [4,5,6,7,8,9,10,11] Despite this heterogeneity, few prognostic and predictive biomarkers are clinically relevant [12, 13], and potentially in conjunction with this heterogeneity, new alternative therapeutic approaches have yet to prove their clinical utility. Further studies show that EMX2 suppresses cell proliferation and is down

Methods

Results

Discussion

Conclusion