Glioblastoma (GBM) remains incurable despite the overwhelming discovery of 2-dimensional (2D) cell-based potential therapeutics since the majority of them have met unsatisfactory results in animal and clinical settings. Incremental empirical evidence has laid the widespread need of transitioning 2D to 3-dimensional (3D) cultures that better mimic GBM's complex and heterogenic nature to allow better translation of pre-clinical results. This systematic scoping review analyses the transcriptomic data involving 3D models of GBM against 2D models from 22 studies identified from four databases (PubMed, ScienceDirect, Medline, and Embase). From a total of 499 genes reported in these studies, 313 (63%) genes were upregulated across 3D models cultured using different scaffolds. Our analysis showed that 4 of the replicable upregulated genes are associated with GBM stemness, epithelial to mesenchymal transition (EMT), hypoxia, and migration-related genes regardless of the type of scaffolds, displaying close resemblances to primitive undifferentiated tumour phenotypes that are associated with decreased overall survival and increased hazard ratio in GBM patients. The upregulation of drug response and drug efflux genes (e.g. cytochrome P450s and ABC transporters) mirrors the GBM genetic landscape that contributes to in vivo and clinical treatment resistance. These upregulated genes displayed strong protein-protein interactions when analysed using an online bioinformatics software (STRING). These findings reinforce the need for widespread transition to 3D GBM models as a relatively inexpensive humanised pre-clinical tool with suitable genetic biomarkers to bridge clinical gaps in potential therapeutic evaluations.
Glioblastoma (GBM) mesenchymal (MES) transition can be regulated by long non-coding RNAs (lncRNAs) via modulation of various factors (Epithelial-to-Mesenchymal (EMT) markers, biological signalling, and the extracellular matrix (ECM)). However, understanding of these mechanisms in terms of lncRNAs is largely sparse. This review systematically analysed the mechanisms by which lncRNAs influence MES transition in GBM from a systematic search of the literature (using PRISMA) performed in five databases (PubMed, MEDLINE, EMBASE, Scopus, and Web of Science). We identified a total of 62 lncRNAs affiliated with GBM MES transition, of which 52 were upregulated and 10 were downregulated in GBM cells, where 55 lncRNAs were identified to regulate classical EMT markers in GBM (E-cadherin, N-cadherin, and vimentin) and 25 lncRNAs were reported to regulate EMT transcription factors (ZEB1, Snai1, Slug, Twist, and Notch); a total of 16 lncRNAs were found to regulate the associated signalling pathways (Wnt/β-catenin, PI3k/Akt/mTOR, TGFβ, and NF-κB) and 14 lncRNAs were reported to regulate ECM components (MMP2/9, fibronectin, CD44, and integrin-β1). A total of 25 lncRNAs were found dysregulated in clinical samples (TCGA vs. GTEx), of which 17 were upregulated and 8 were downregulated. Gene set enrichment analysis predicted the functions of HOXAS3, H19, HOTTIP, MEG3, DGCR5, and XIST at the transcriptional and translational levels based on their interacting target proteins. Our analysis observed that the MES transition is regulated by complex interplays between the signalling pathways and EMT factors. Nevertheless, further empirical studies are required to elucidate the complexity in this process between these EMT factors and the signalling involved in the GBM MES transition.