Zinc Finger E-Box Binding Homeobox Family: Non-Coding RNA and Epigenetic Regulation in Gliomas

Abstract

Gliomas are the most common malignant brain tumours. Among them, glioblastoma (GBM) is a grade four tumour with a median survival of approximately 15 months and still limited treatment options. Although a classical epithelial to mesenchymal transition (EMT) is not the case in glioma due to its non-epithelial origin, the EMT-like processes may contribute largely to the aggressive and highly infiltrative nature of these tumours, thus promoting invasive phenotype and intracranial metastasis. To date, many well-known EMT transcription factors (EMT-TFs) have been described with clear, biological functions in glioma progression. Among them, EMT-related families of molecules such as SNAI, TWIST and ZEB are widely cited, well-established oncogenes considering both epithelial and non-epithelial tumours. In this review, we aimed to summarise the current knowledge with a regard to functional experiments considering the impact of miRNA and lncRNA as well as other epigenetic modifications, with a main focus on ZEB1 and ZEB2 in gliomas. Although we explored various molecular interactions and pathophysiological processes, such as cancer stem cell phenotype, hypoxia-induced EMT, tumour microenvironment and TMZ-resistant tumour cells, there is still a pressing need to elucidate the molecular mechanisms by which EMT-TFs are regulated in gliomas, which will enable researchers to uncover novel therapeutic targets as well as improve patients’ diagnosis and prognostication.