internal ribosome entry site; LARP4, La-related protein 4; LATS1, large tumor suppressor kinase 1; lncRNAs, long noncoding RNAs; MIBC, muscle invasive bladder cancer; miRNA, microRNA; ncRNAs, noncoding RNAs; NF1, neurofibromin 1; Notch1, notch homolog 1; NSCLC, non-small cell lung cancer; OS, overall survival; PCK1, phosphoenolpyruvate carboxykinase 1; PDAC, pancreatic ductal adenocarcinoma; RBP, RNA-binding protein; RCAN1, regulation of Down syndrome critical region gene 1; sncRNAs, short noncoding RNAs; TIMP3, metalloproteinase inhibitor 3; USP28, ubiquitin-specific peptidase 28; YBX1, Y box binding protein 1.
AbstractCircular RNAs (circRNAs) have a covalently closed circular conformation and are structurally stable. Those circRNAs with tumor-suppressive properties play an important role in tumorigenesis and metastasis and thus may be used as therapeutic targets of cancers. Herein, we review the current understanding of the classification of circRNAs and summarize the functions and mechanisms of circRNAs that have tumor-suppressive roles in various cancers, including liver cancer (circARSP91, circ-ADAMTS13, circADAMTS14, circMTO1, hsa_circ_0079299, and circC3P1), bladder cancer (circFNDC3B, circITCH, circHIPK3, circRNA-3, cdrlas, and circLPAR1), gastric cancer (circLARP4, circYAP1, hsa_cric_0000096, hsa_circ_0000993, and circPSMC3), breast cancer (circ_000911, hsa_circ_0072309, and circASS1), lung cancer (hsa_ circ_0000977, circPTK2, circ_0001649, hsa_circ_100395, and circ_0006916), glioma (circ_0001946, circSHPRH, and circFBXW7), and colorectal cancer (circITGA7 and hsa_circ_0014717). Thanks to their structural stability, these tumor-suppressive cir-cRNAs may be used as potential and potent therapeutic targets. Moreover, we propose a new method for the classification of circRNAs. Based on whether they can be translated, circRNAs can be divided into noncoding circRNAs and coding circRNAs.
K E Y W O R D Sbiogenesis, cancer, circular RNA, mechanism, therapeutic target
| INTRODUC TI ONThose RNAs that do not encode proteins are called ncRNAs. 1 Regulatory ncRNAs are divided into lncRNAs and sncRNAs. LncRNAs can be linear or circular. 2 Circular RNAs were first discovered in 1976. 3 Since then, a variety of circRNAs have been discovered. 4,5 CircRNAs are more resistant to exonuclease and are more stable than other lncRNAs. 3,6 They exist in exosomes and plasma. 6,7 Li et al identified more than 1000 circRNAs in human serum exosomes. 6 Li et al found 343 differentially How to cite this article: