Regulation of EMT Markers, Extracellular Matrix, and Associated Signalling Pathways by Long Non-Coding RNAs in...

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.