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].