Notch Signaling Pathway
The Notch signalling pathway is an evolutionary conserved intercellular
pathway that governs various physiological and developmental processes
such as tissue homeostasis, stem cell maintenance, proliferation,
apoptosis, and cell fate decision
[47]. Several studies have shown a
positive correlation between Notch signaling pathway and lncRNA involved
in various tumor progressions whereby the lncRNA regulates this pathway
by acting as an oncogene or tumor suppressor
[48]. For instance, Wu et
al. (2021) discovered that the lncRNA, HOXA cluster antisense RNA 2
(HOXA-AS2 ) plays a tumour-promoting role in cell proliferation
and migration of cervical cancer by activating Notch pathway
[49]. LncRNA, FAM83H antisense RNA 1
(FAM83H-AS1 ) promotes cell proliferation of colorectal carcinoma
and is linked to poor prognosis by regulating the Notch pathway
[50]. In a study by Liu et al.[37] they found that the lncRNA,
small nucleolar RNA host gene 1 (SNHG1 ), enhances progression of
laryngeal cancer in cell proliferation by modulating Notch1 pathway
[35].
In glioma, overexpression of Notch receptors occurred, and activation of
the Notch pathway plays a critical oncogenic role by contributing to
brain tumours’ growth, survival, invasion and recurrence
[51]. The most frequent somatically
mutated gene in more than 2900 tumors; Endometrial cancer (n = 248),
prostate cancer (n = 112), large intestine (n = 224), esophageal cancer
(n = 146), lung cancer (n = 230), glioblastoma (n = 291), ovarian cancer
(n = 316), skin cancer (n = 121), liver cancer (n = 231), pancreatic
cancer (n = 99), breast cancer (n = 507) and renal cancer (n = 424) are
as follows; Notch-1 (7.3%), Notch-2 (7.0%), Notch-3 (5.9%) and
Notch-4 (5.6%) [52]. Research by
Wang et al. (2018) reported that upregulation of prostate
cancer-up-regulated long non-coding RNA 1 (PlncRNA-1) might promote
glioma development and progression by activating the Notch pathway
through modulation of several Notch signal-related protein expressions,
including Notch-1, Jagged 1 and HES family bHLH transcription factor 1
(Hes-1) [48]. As for the correlation
between lncRNA ZFAS1 and Notch pathway in glioma, Gao et
al. [18] discovered the inhibition
of ZFAS1 significantly reduced the expression of two Notch
signal-relate proteins, Hes-1 and notch intracellular domain (NICD)
[18], where both proteins have
crucial roles in Notch pathway [53].
This result suggested that ZFAS1 could be another key activator
for the Notch pathway, facilitating glioma progression. However, the
exact mechanism by which ZFAS1 activates the Notch pathway is
still unknown, whether directly or indirectly
[13].
The general outcome of ZFAS1 upregulation in glioma cells is depicted in
Figure 2. Figure 3 shows how high ZFAS1 expression in gliomas can affect
the activities of glioma cells, with miRNA sponging inhibiting cell
apoptosis and cisplastin cytotoxicity, and decreasing patient survival.
Additionally, it summarises the impact of ZFAS1 expression on glioma
cell metabolisms. For instance, it increases glucose uptake by glioma
cells, increases cell migration, invasion, and proliferation, and
increases resistance to chemotherapy drugs like TMZ. Furthermore, by
regulating the expression of a protein that’s essential to the
development of gliomas, high ZFAS1 expression can promote the
development of gliomas through the EMT and Notch signalling pathways.