The circRNA–microRNA code: emerging implications for cancer diagnosis and treatment

Abstract

Circular RNA s (circ RNA s) comprise an emerging new class of endogenous RNA s expressed abundantly by the eukaryotic transcriptome. They are characterized by a covalently closed loop structure, resulting in RNA molecules that are more stable than linear RNA s. A growing number of studies indicate that circ RNA s play critical roles in human diseases and show great potential as biomarkers and therapeutic targets. The molecular events determined by circ RNA activity, the circ RNA code, involve other types of noncoding RNA molecules, primarily micro RNA s, long noncoding RNA s, and RNA ‐binding proteins. Herein, we mainly focus on the circ RNA –micro RNA code, showing how this relationship impacts the regulation of gene expression in cancer. The emerging roles for circ RNA s in oncogenic pathways highlight new perspectives for the detailed molecular dissection of cancer pathogenesis and, at the same time, offer new opportunities to design innovative therapeutic strategies. Here, we review recent research advancements in understanding the biogenesis, molecular functions, and significance of circ RNA s in cancer diagnosis and treatment.

Circular RNA hsa_circ_0000654 promotes esophageal squamous cell carcinoma progression by regulating the miR‐149‐5p/IL‐6/STAT3 pathway

“…Studies have indicated that circRNA participates in the regulation of tumor cell progression in a variety of malignancies, including aspects such as proliferation, metastasis, apoptosis, and epithelial-mesenchymal transition. 28,29 For instance, circ_0006528 facilitates human breast cancer progression by activating the MAPK/ERK signaling pathway 30 ; circ_ 0058124 modulates the carcinogenesis and invasion of NOTCH3/GATAD2A papillary thyroid carcinoma with high expression linked to adverse pathological parameters in patients, 31 and circ-PRKCI enhances the proliferation and invasion of ESCC via upregulating AKT3 expression. 32 In this study, we demonstrated that compared with normal tissues, circ_0000654 expression in ESCC tissues was remarkably increased, and its high expression was linked to the higher T stage and lymph node metastasis of ESCC patients.…”

Elevation of circ‐PITX1 upregulates interleukin 17 receptor D expression via sponging miR‐518a‐5p and facilitates cell progression in glioma

“…Several circRNAs show clear evolutionary conservation or strict regulation function, implying that they are of functional importance. [14][15][16] The aberrant expression of circRNA has been found in a wide variety of tumors, including GM. [10][11][12][13] For example, Lei et al 17 revealed that hsa_circ_0076248 could promote GM tumorigenesis through sponging miR-181a and regulate SIRT1 expression.…”

Circ‐MTO1 correlates with favorable prognosis and inhibits cell proliferation, invasion as well as miR‐17‐5p expression in prostate cancer

“…Circular RNAs (circRNAs), a novel class of non‐coding RNAs presenting with closed loops without poly A tails, are stably expressed in human and have almost no protein‐coding function . In recent years, circRNAs have been revealed as genetic factors that play critical roles in various cancers, such as promoting cancer progression by regulating cancer cell functions and presenting with potential as prognostic biomarkers . Additionally, circRNAs are increasingly implicated in prostate cancer as well; however, the relevant studies are not as abundant as the studies of other cancers .…”

“…8 In recent years, circRNAs have been revealed as genetic factors that play critical roles in various cancers, such as promoting cancer progression by regulating cancer cell functions and presenting with potential as prognostic biomarkers. [9][10][11] Additionally, circRNAs are increasingly implicated in prostate cancer as well; however, the relevant studies are not as abundant as the studies of other cancers. 12,13 Circular RNA-mitochondrial tRNA translation optimization 1 (circ-MTO1) is a novel circRNA that is previously reported as an anti-tumor gene, which inhibits liver fibrosis to prevent hepatocellular carcinoma and represses progression of lung cancer and breast cancer.…”