Epithelial-to-Mesenchymal Transition
EMT is a biological process that transforms epithelial cells into mesenchymal cells by losing cell polarity and junctions while gaining the ability to migrate, invade, proliferate, and differentiate into a particular cell types [38]. EMT also can make epithelial tumour cells migrate and invade without impairing their viability [38]. EMT can be classified into three subtypes based on the context in which it occurs: EMT type 1, EMT type 2, and EMT type 3, with EMT type 3 being associated with subsets of tumour cells that undergo phenotypic changes to promote migration, invasion, and metastasis[39]. In EMT type 3, the formation of metastatic tumour nodules occurs at distant sites as a result of some tumour cells with a transitional mesenchymal phenotype that undergoes mesenchymal-epithelial transition (MET), a reverse conversion of EMT [40].
The EMT process activation by tumour microenvironment (TME) stimuli has been considered a crucial process for tumour cells to gain their highly malignant phenotypes[41]. Once the formation of TME is established, Unfolded Protein Response (UPR) aids tumour cells in epithelial to EMT by overcoming the stress of cell detachment, and also increases EMT transcription factor expression and reduces cell–cell junction markers, promoting metastasis [42]. EMT is highly related with glioma malignancy[43], and lncRNAs have been identified to coordinate various cellular processes in many tumour cells, including glioma cells, through EMT regulation[44].
Key EMT protein markers were reported to be increased by overexpression of ZFAS1 which in turn promoted the development of glioma [45]. Several key EMT markers, including N-cadherin, MMP2, MMP9, ZEB1 , Integrin β1, Twist, and Snail, exhibited a significant reduction in expression when ZFAS1was knocked down, whereas E-cadherin expression increased [45]. These results were similar to Gao et al. [18] findings, where suppression of ZFAS1 led to a significant decrease in the expression level of EMT-related proteins (N-cadherin and Snail), and an increase in E-cadherin [46]. Lvet al. [19] investigated whether ZFAS1 influenced EMT in 69 glioma tissues by using Pearson’s correlation analysis to examine the link between ZFAS1expression and EMT markers. The findings showed a positive correlation between several EMT markers (N-cadherin, ZEB1 , Integrin β1 and Twist) and ZFAS1 ’s expression, while a negative correlation between E-cadherin and ZFAS1 ’s expression was observed. Thus, these findings suggested ZFAS1 could enhance malignant glioma’s migration and invasion by inducing the EMT process [45].