MEOX2 Transcription Factor Is Involved in Survival and Adhesion of Glioma Stem-like Cells

Abstract

The high expression of MEOX2 transcription factor is closely associated with poor overall survival in glioma. MEOX2 has recently been described as an interesting prognostic biomarker, especially for lower grade glioma. MEOX2 has never been studied in glioma stem-like cells (GSC), responsible for glioma recurrence. The aim of our study was to investigate the role of MEOX2 in GSC. Loss of function approach using siRNA was used to assess the impact of MEOX2 on GSC viability and stemness phenotype. MEOX2 was localized in the nucleus and its expression was heterogeneous between GSCs. MEOX2 expression depends on the methylation state of its promoter and is strongly associated with IDH mutations. MEOX2 is involved in cell proliferation and viability regulation through ERK/MAPK and PI3K/AKT pathways. MEOX2 loss of function correlated with GSC differentiation and acquisition of neuronal lineage characteristics. Besides, inhibition of MEOX2 is correlated with increased expression of CDH10 and decreased pFAK. In this study, we unraveled, for the first time, MEOX2 contribution to cell viability and proliferation through AKT/ERK pathway and its potential involvement in phenotype and adhesion properties of GSC.

RING Finger Protein 10 Regulates AP-1/Meox2 to Mediate Pirarubicin-Induced Cardiomyocyte Apoptosis

“…There is no Meox2 expression in the early stage of heart development and only in the relatively late stage of heart development; that is, when the proliferation of cardiac cells begins to decline, Meox2 begins to be expressed [42]. Meox2 is involved in a variety of cellular processes, including cell differentiation and apoptosis [43,44]. The expression of RNF10 enhanced Meox2-mediated activation of the p21WAF1 promoter, indicating that RNF10 is an activator of Meox2 [20,45].…”

Definition and verification of novel metastasis and recurrence related signatures of ccRCC: A multicohort study

“…Reduced MEOX2 expression has been shown to be significantly correlated with short OS in hepatocellular and larynx carcinoma, whereas in lung cancer, MEOX2 overexpression has been demonstrated to be correlated with chemoresistance [ 64 ]. Tachon et al [ 65 ] discovered that MEOX2 was one of the transcription factors associated with OS in glioma. In addition, MEOX2 contributed to cell viability and proliferation through the AKT/extracellular‐signal‐regulated kinase pathway and was involved in regulating the phenotype and adhesion properties of cancer stem cells [ 66 ].…”

Integrated Analysis Identifies MEOX2 as a Malignant Driver and Prognostic Biomarker in Brain Glioma

“…As for glioma, previous studies showed that MEOX2 expression was signi cantly correlated with OS, and may serve as a prognostic predictor (Tachon et al 2019). Recently, two independent groups demonstrated that MEOX2 regulates glioma proliferation, motility, and glioma stem cell survival (Tachon et al 2021;Wang et al 2022). However, the repertoire of MEOX2 on glioma was still largely unknown.…”

“…MEOX2, a homeobox transcriptional factor, is located at the 7p21.2 locus and reported to have a dual role in several types of peripheral cancers (Ávila-Moreno et al 2014; Tian et al 2018). Recently, two independent groups demonstrated the effects of MEOX2 on glioma growth (Wang et al 2022) and glioma stem cell survival (Tachon et al 2021). However, the expression pattern and biological functions of MEOX2 in GBM remain not fully understood.…”