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Gene & Protein in Disease circRNAs and cancer

such as chromatin modifications, DNA methylation, discussion on the functional mechanisms of circRNAs
gene transcription, and messenger RNA (mRNA) destiny and their dysregulation in several cancers. In addition,
regulators splicing, translation, or decay [3-8] . this paper highlights the gaps, opportunities, and
Although circRNA biogenesis has been previously challenges in using circRNA-based approaches for cancer
reviewed , the specific mechanisms of circRNAs treatment. Moreover, the clinical applications of circRNAs
[9]
formation are still poorly understood in terms of being in developing liquid biopsy biomarkers and identifying
explored and validated regularly. Most of the discovered promising biomarkers for cancer diagnosis, prognosis,
exonic circRNAs (>90%) originated from protein-coding and therapy are also well discussed. Considering the
genes with one or several exons that have substantially need for literature and novelty aspects in this domain,
longer intracellular half-lives, which implicates that we anticipate that the current review will be a resourceful
circRNAs are resistant to exonuclease digestion [10-12] . addition of literature on circRNAs research and their
Certain features of circRNAs include: (1) circRNAs are future perspective regarding diagnosis and anticancer
abundantly available in human fluids and tissues, and due therapies.
to their stable covalently closed structure, certain circRNAs 2. Regulatory role of circRNAs in cancer
gather at a significant level compared to their canonical
[13]
linear mRNAs ; (2) numerous circRNAs in eukaryotes CircRNA altered expression is connected with diabetes,
are conserved evolutionarily ; and (3) many circRNAs atherosclerosis, cardiovascular disease, and neurological
[14]
are explicitly expressed in tissues or cells [14,15] . illnesses based on its developing involvement in
gene regulation [26] . However, recent research has
In addition, by competing for the particular miRNA,
RNA species such as lncRNAs, pseudogene transcripts, demonstrated the aberrant production of circRNAs in
several cell types of cancer, including gastric cancer (GC)
mRNAs, and circRNAs that serve as competing endogenous [27] , colorectal cancer (CRC) [28] , hepatocellular carcinoma
RNAs (ceRNAs) affect genomic expression post- (HCC) [29] , breast cancer (BC) [30] , glioblastoma [31] , and
transcriptionally and impact the half-life or translation [32]
of target RNAs [16,17] . CircRNAs have been revealed to act ovarian cancer (OC) . Along the same lines, circRNAs
like ceRNAs, regulating important biochemical events in participate in the modulation of many cellular signaling
[33]
cancer such as cell division, angiogenesis, and apoptosis. pathways, which can modulate tumorigenesis . Most
For example, it has been demonstrated that circRNAs can circRNAs have potential binding sites and act as sponges
act as ceRNAs by controlling the expression of the GDNF for the different miRNAs to regulate miRNA mediating
family receptor alpha-1 (GFRA1) to change the expression the downstream activation of the target genes implicated
of miR-34a, which subsequently inhibits the apoptosis of in cancers. CircRNAs feature a covalently closed ring
triple-negative breast cancer (TNBC) [17,18] . CircRNAs can structure that is difficult to be degraded by cellular
also be utilized as RNA-binding protein (RBP) decoys to exonuclease degradation mechanism which typically
[12]
mediate its host gene expression or to subtly influence readily recognizes the terminals of linear RNAs [25] .
the activities of RBPs and associated proteins [14,19] . Exosomes are also enriched with stable circRNAs .
Furthermore, certain circRNAs containing IRES-like Considering the wide availability, cell-and-tissue-
components and start codon (AUG) sites enable them to specific expression, and better stability, determining
translate into particular small proteins/peptides . their function in human illness, particularly cancer, has
[20]
been the main focus of many researchers.
Some circRNAs are obviously linked to cancer patients’
clinical outcomes due to their crucial roles in biological 2.1. BC
pathways . However, circRNAs can also play opposing roles BC is a diverse illness and the world’s most significant
[21]
to their linear counterparts. For example, the linear RNA cause of mortality . Evidence shows that oncogenic or
[34]
of the human and mouse ZBTB7A genes works as a tumor tumor suppressor properties are influenced by circRNAs
suppressor, but the circRNA generated by ZBTB7A genes has in BC [35,36] . Overexpression of circRNAs was found in
[22]
a carcinogenic role in connective tissue malignancies . On estrogen-positive (ER+) adjacent normal tissues than in
the other hand, the formation of FOXO3-encoded proteins, ER-negative tumor samples in the Cancer Genome Atlas
such as those caused by the mouse or human FOXO3 (TCGA) database, implying that the frequency of circRNAs
gene, induces apoptosis and suppress tumor formation . could serve as a possible cell proliferation indicator in
[23]
Moreover, circRNAs in exosomes and body fluids can serve BC . Another highly expressed circRNA in BC, circ-
[37]
as potential disease biomarkers [21,24,25] . DNMT1 (hsa_circRNA_102439), was reported to increase
Given the worth and interest of creating circRNAs- cell proliferation and autophagy and inhibit senescence
based knowledge, this paper aims to provide a detailed by binding directly to p53 and AUF1, resulting in the

Volume 1 Issue 2 (2022) 2 https://doi.org/10.36922/gpd.v1i2.138