The biogenesis and biological functions of circular RNAs and their molecular diagnostic values in cancers

Abstract

Background In addition to non‐coding RNAs (lncRNAs) and microRNAs (miRNAs), circular RNAs (circRNAs) are endogenous RNAs with various functions, which have recently become a research hotspot. CircRNAs are a kind of closed circular RNA molecule widely existing in transcriptomes. Due to lack of free ends, they are not easily cleaved by RNase R, thus avoiding degradation. They are more stable than linear RNAs. Methods Data were collected through PubMed. The following search terms were used: “circular RNA,” “circRNA,” “cancer,” “mechanism,” “biogenesis,” “biomarker,” “diagnosis.” Only articles published in English were included. Results Most circRNAs express tissue/developmental stage specificity. Moreover, circRNAs are involved in the regulation of a variety of biological activities. In this review, we discuss the formation, classification, and biological functions of circRNAs, especially their molecular diagnostic values in common cancers, including gastric cancer (hsa_circ_002059, circ_LARP4, hsa_circ_0000190, hsa_circ_0000096, circ‐SFMBT2, and circ_PVT1), hepatocellular carcinoma (circ_104075, circRNA_100338, circ_MTO1, and circZKSCAN1), colorectal cancer (hsa_circ_0136666 and hsa_circ_0000523), lung cancer (hsa_circ_0006427, circ_100876, and circ_ABCB10), breast cancer (hsa_circ_0089105, circAGFG1, and circEPSTI1), bladder cancer (circFNDC3B and circTFRC), and esophageal squamous cell carcinoma (circ_100876 and circ‐DLG1). Conclusion CircRNAs not only play important roles in tumorigenesis, but also may become new diagnostic biomarkers.

Circular RNA SMARCA5 may serve as a tumor suppressor in non‐small cell lung cancer

“…Although these studies display downregulated expressions of circ‐SMARCA5 in some cancers, the involvement of circ‐SMARCA5 in lung cancer has not been clearly clarified, and only one study shows that circ‐SMARCA5 is downregulated in NSCLC tissues compared to the adjacent normal tissues, and it inhibits cell proliferation, migration as well as invasion in NSCLC cell lines . Some recent studies have implied that non‐coding RNAs, especially circRNAs, play crucial roles in pathology and progression of NSCLC . For example, long non‐coding RNA KDM5B anti‐sense RNA 1 enhances tumor progression in NSCLC; circular RNA F‐circSR derived from SLC34A2‐ROS1 fusion gene enhances cell migration in NSCLC; overexpression of circular RNA FARSA promotes NSCLC cell migration and invasion .…”

Circ_DLG1 facilitates esophageal squamous cell carcinoma progression by mediating miR-338-3p/MAP3K9 axis via activating MAPK/ERK pathway

“…The most studied function of circRNAs is acting as miRNA sponges to modulate the expression of downstream mRNA, thus participating in biological processes, such as tumor development [29]. Here, miR-338-3p was identi ed as a target of circ_DLG1, and miR-338-3p directly bound to MAP3K9.…”

Circular RNA SMARCA5 correlates with favorable clinical tumor features and prognosis, and increases chemotherapy sensitivity in intrahepatic cholangiocarcinoma

“…Until now, there are only preliminary investigations focusing on the role of circRNAs in cancers . Existing evidence demonstrates that circRNA expression is abnormal expressed in tumor tissues compared with adjacent tissues, and associated with clinical outcomes in patients with tumors . For example, CircRNA PTPRM expression is significantly increased in HCC tissues compared with paired adjacent tissues, and its overexpression is correlated with HCC recurrence and metastasis in HCC patients .…”