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Gene & Protein in Disease circRNAs and cancer

Acute myeloid leukemia, chronic myeloid neoplasms, demonstrated significant potential as circulating diagnostic
chronic lymphocytic leukemia (CML), B- and T-cell biomarkers for liquid biopsy using cell-free RNA-based
lymphoma, and multiple myeloma (MM) are hematological liquid biopsy. CircRNAs have several essential features
malignancies that exhibit circRNA expression. Hsa_ including stability, specificity, conservation, and abundance
circ_0004277 was downregulated in AML samples as in bodily fluid, making them valuable biomarkers for
opposed to controls and post-treatment subjects. By human diseases, including cancer. CircRNAs can be
acting as a sponge for miR-138-5p and miR-30c-1-3p, found in various human body fluids, including saliva,
hsa_circ_0004277 controls the expression of downstream brain/spinal fluid, blood, urine, free-floating cells (such as
genes implicated in cancer development [101] . CircPVT1 was circulating blood cells/tumor cells), and exosomes [112,114,116] .
increased in acute myeloid leukemia compared to normal Circulating cell-free RNAs released by various tissues and
bone marrow cells, and it was discovered that it acts as a cells can be recognized in serum, plasma, and blood. In
sponge for the miRNA let-7, showing that it might be a addition, the stability of circRNA is an important factor,
viable treatment focus for the disease [102] . Several circRNAs leading to potential target for many diseases [117] . As a
with abnormal expression in CML have been identified result, cell-free circRNAs have tissue-specific features,
using high-throughput sequencing technology. Among emphasizing their clinical significance for the respective
these circRNAs, hsa_circ_0080145 was significantly tissues [118] . Microarray, NanoString technology, digital
overexpressed and can effectively bind to miR-29b to droplet PCR (ddPCR), or next-generation sequencing
regulate cell proliferation in CML [103] . Besides, circ-CBFB (NGS) technologies can be used to quantify circRNAs
was overexpressed in CLL patients’ samples compared derived from different body fluids, circulating blood cells,
to normal controls. It promotes cell cycle progression or exosomes for early diagnosis, disease development and
and reduction by inhibiting miR-607, facilitating FZD3 monitoring, or precise therapy selection for different types
expression, and activating the Wnt/b-catenin pathway in of cancers (Figure 1) [119-121] . In liver cancer cells and cell-
CLL [104] . By performing RNA sequencing profiling, Dahl et derived exosomes, a 2-fold enrichment of circRNAs was
al. recently identified a novel overexpressed circRNA from recently discovered in exosomes compared to parental
the IKZF3 gene with oncogenesis functions [105,106] . cells, and the expression can be persistent in serum after
incubation at room temperature for up to 24 h . circFMN2
[25]
Several other differentially expressed circRNAs have and circIFT80 have recently been shown to be highly
also been studied, and their upregulation is associated overexpressed in serum exosomes and have been linked
with the progression of different cancers. For instance, to cell proliferation, invasion, and inhibition of apoptosis
circTCF25 in bladder cancer [107] , hsa_circ_100855 in through the circFMN2/miR-1182/hTERT axis and the
laryngeal cancer [108] , circUBAP2 in osteosarcoma [109] , circIFT80/miR-1236-3p/HOXB7 axis, respectively [122,123] .
circ-ZNF609 in renal cell carcinoma [110] , circSLC30A7 in Cell-free circRNAs’ roles in human bodily fluids and
oral squamous cell carcinomas [111] , and all of which are their implications in numerous diseases might be used
upregulated and involved in the progression of cancers. as liquid biopsy biomarkers to identify tumors at an early
In contrast, Cir-ITCH is less expressed in esophageal stage. Table 1 enumerates the circRNAs identified to be
squamous cell carcinoma than in the adjacent normal dysregulated in different human body fluids.
tissues . Therefore, based on the widespread presence of
[50]
circRNAs in various parts of the human body, it is logical 4. CircRNAs involved in drug resistance
to propose that circRNAs can be used in cancer diagnosis.
Many studies have linked ncRNAs (lncRNAs and miRNAs)
3. CircRNAs as diagnostic biomarkers for to chemoresistance [150,151] , paucity of data is available on
cancer the regulatory mechanisms of circRNAs in developing
drug resistance in malignancies. Some studies have
Different sampling strategies can be used to diagnose recently looked at the function of circRNAs in resistance
the etiologic modulator of cancer. In a liquid biopsy, to various anticancer medicines (chemotherapeutic drugs,
body fluid was used as a sample for diagnosis or the targeted therapies, and immunotherapeutic drugs) in
development of human diseases instead of tissue biopsy, terms of concentration of drug, downstream signaling
with the advantages of being less intrusive, accurate, easy pathway regulation, and DNA repair ability [152,153] . Drug
assessments, time serving, and with a lower morbidity resistance phenotypes can have two mechanisms: intrinsic
rate [112] . Several liquid biopsy biomarkers have been proved or acquired, depending on whether they were innately
helpful in the diagnosis of various malignancies, including resistant to treatment or tolerated after drug exposure. Due
cell-free DNA [113] , circulating tumor DNA [112] , and cell- to their high differentiation rates, cancer stem cells can also
free RNA [113-115] . NcRNAs, particularly circRNAs, have drive acquired resistance. As a result, tumor heterogeneity,

Volume 1 Issue 2 (2022) 6 https://doi.org/10.36922/gpd.v1i2.138