Page 50 - GPD-1-2

Gene & Protein in Disease circRNAs and cancer

promotion of nuclear translocation of these proteins . 2.3. GC
[38]
Similarly, FECR1, a novel circular RNA generated from the GC is a major source of mortality and a significant financial
FLI1 gene, regulates DNA methylation/demethylation of burden on health-care systems worldwide . CircRNAs are
[48]
target genes to mediate BC cell metastasis [7,39] . In addition, reported to be stable in plasma and gastric juice, making
the increase expression of circAGFG1 in TNBC increases them an ideal diagnostic marker for GC. Three circRNAs
cell proliferation, migration, invasion, tumor development, (has_circ_002059, hsa_circ_0000190, and circ-0001649)
and metastasis by serving as ceRNA for miR-195-5p to are variably expressed in the plasma of post-operative GC
diminish its target genes’ inhibitory function [40,41] . patients compared to pre-operative GC individuals. They
On the contrary, circFOXO3 is significantly lowered are considerably downregulated in GC tissues compared
[49]
in BC tissues compared to the adjacent normal ones . to nearby tissues with average physiological properties .
[36]
Abnormal circ-FOXO3 triggers programmed death and The reduced expression of the above three circRNAs
prevents tumor cell development. On the other hand, correlates significantly with gender, age, distal metastasis,
overexpression of circFOXO3 leads to the increase of and TNM stage [50-52] . However, circHIPK3, but not HIPK3
its parental gene expression and upregulates the genes mRNA, is upregulated in GC and significantly affects
responsible for cell deaths. For example, PUMA inhibits cell proliferation. CircHIPK3 expression is substantially
p53 expression and promotes MDM2-induced p53 higher than HIPK3 mRNA, thus it demonstrates its crucial
[19]
degradation. In addition, circ-CCNB1 is significantly role as a product of pre-HIPK3 mRNA . CircPVT1,
suppressed in BC. It has been demonstrated that circ- overexpressed in GC, has been identified to promote cell
CCNB1 in p53 mutant cells forms a compound with proliferation. Mortality risk and time without developing
H2AX and BCLAF1 mediating apoptosis . In TNBC, the an illness positively correlate with its interaction with miR-
[39]
[27]
downregulation of circTADA2A-E6 inhibits proliferation, 125 in GC patients . CircPVT1 mediates its function by
motility, and infiltration. circTADA2A-E6 serves as a miR- upregulating c-Myc oncoprotein levels in GC cells and acts
203a-3p sponge and restores the production of miRNA as a sponge for let-7b. CircRNAs are expressed differently,
targeting the SOCS3 gene, leading to the less invasive they interact with miRNAs through their binding sites to
neoplastic phenotype. It concludes that circRNAs can control the transcription of their downstream targets and
may serve as a novel biomarker for GC .
[53]
mediate BC by acting as oncogenes or suppressors.
2.4. CRC
2.2. OC
A study showed a negative correlation between the total
OC is a highly aggressive tumor among gynecological circRNAs abundance and cell proliferation in CRC, where
malignancies and is primarily diagnosed in advance . its high expression suppressed cell proliferation . The
[42]
[32]
Multiple cancer-related signaling pathways, usually circ-ITCH was significantly lowered in CRC tissues.
activated by linear mRNA, can be downregulated by Its deficiency upregulated ITCH expression, which
circRNAs, indicating a potential role of circRNAs in tumor blocked the Wnt/beta-catenin pathway . However,
[54]
activation or inhibition . CircRNAs exhibit differential circ_0060745 was upregulated in CRC and linked
[43]
expression among OC patients and healthy individuals, with cellular propagation and metastasis through the
showing their potential roles as both the therapeutic sequestering of miR-4736 and elevation of CSE1L levels .
[55]
and diagnostic biomarkers for this disease . Ning et al. Similarly, an analysis of 50 CRC tissue samples revealed
[44]
investigated circRNAs expression in EOC tissue samples that hsa_circ_0007142 is upregulated and linked with
and identified that 2556 circRNAs are upregulated, poor differentiation, and metastasis to the lymph nodes is
and 1832 circRNAs are downregulated compared with mediated by its binding to miR-103a-2-5p . Furthermore,
[56]
normal ovarian tissue samples . Moreover, among the circ-BANP is overexpressed in CRC tissues, and its
[45]
dysregulated circRNAs, circEXOC6B and circN4BP2L2 silencing suppresses cellular multiplication . Other
[57]
were suggested to possess a potential prognostic disease- circRNAs reported to be upregulated in CRC include ciRS-
specific biomarker. Similarly, hsa_circ_0061140 has also 7 , circCCDC66 , and has_circ_0000069 . They are
[28]
[59]
[58]
been elevated in OC cells, which directly controls FOXM1 also associated with clinicopathological variables such as
expression by binding to miR-370, thus promoting cell age and TNM stage. According to Zhang et al.’s research of
proliferation, migration, and epithelial-mesenchymal the human circRNAs array in CRC tissues, hsa circRNAs
transition (EMT) . However, CircHIPK3 (hsa_ 103809 and 104700 were dramatically downregulated
[46]
circ_0000284) is substantially related to multiplication, and associated with lymph nodes, tumors, and distant
motility, invasive, and apoptosis inhibition through metastasis . CircRNAs are expressed differently to
[60]
binding to miR-10-5p . mediate cancer development.
[47]
Volume 1 Issue 2 (2022) 3 https://doi.org/10.36922/gpd.v1i2.138