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

Abstract

Purpose: Glioma is a common type of malignant tumor in the brain, of which glioblastoma (GBM) is the most aggressive and lethal form. Despite current progress in the clinical treatment, the prognosis of GBM is still not satisfied, mainly due to the genomic alternations and complicated gene regulatory network. MEOX2 was originally identified as a homeobox transcriptional factor, that was reported to play a role in several types of cancers. However, the expression pattern and biological functions of MEOX2 in glioma are not well elucidated. This study aims to clarify the role of MEOX2 in glioma.Methods: Bioinformatic analysis from TCGA and CGGA databases was used to investigate the correlation of MEOX2 with glioma malignancy and clinical prognosis. The expression of MEOX2 was confirmed from clinical samples by qPCR and western blot. Lentivirus-mediated MEOX2 overexpression and knockdown were employed to investigate the biological functions of MEOX2 in glioma malignant behaviors. RNA-seq and signaling investigations were performed to reveal the molecular mechanisms.Results: Bioinformatic data from public databases and our cohort showed that MEOX2 expression was highly associated with glioma malignancy and could predict the poor prognosis. MEOX2 positively regulates glioma cell proliferation, migration/invasion and chemoresistance to temozolomide. Mechanistically, MEOX2 regulates gene profiles related to PI3K/AKT/mTORC1 pathways and thus promotes glioma malignancy.Conclusion: Our work identifies the novel function of MEOX2 in gliomas, and provides a potential target for glioma prognosis and clinical interventions.