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Aging and disease
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Biogenesis, features, functions, and disease relationships of a specific Circular RNA: CDR1as
Ziyuan Guo, Qidong Cao, Zhuo Zhao, Chunli Song*
Department of Cardiovascular Internal Medicine, the Second Hospital of Jilin University, Changchun, China
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Abstract  

In 2011, Hansen discovered the natural antisense transcript (NAT) of the cerebellar degeneration-related protein 1 gene (CDR1), and further described CDR1 NAT as a circular RNA (CircRNA). CDR1 antisense RNA (CDR1as), which is the official name of CDR1 NAT, is conserved and extensively expressed in most eutherian mammal brains and other specialized tissues. Further studies have elucidated its biogenesis, features, functions, and relationships with diseases. CDR1as is involved in many disease processes as a microRNA (miR) sponge. Therefore, it seems that further research on CDR1as could facilitate the diagnosis and treatment of some diseases, such as cancer and diabetes. However, a detailed analysis of the results of studies on CDR1as revealed that they are inconsistent and make unclear conclusions. In this review, we gathered and analyzed the recent studies about CDR1as in detail and aimed to elucidate accurate conclusions from them.

Keywords CDR1as      sponge      miR-7      biogenesis      functions.     
Corresponding Authors: Chunli Song   
About author:

These authors contributed equally to this work.

Just Accepted Date: 20 October 2019  
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Ziyuan Guo
Qidong Cao
Zhuo Zhao
Chunli Song
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Ziyuan Guo,Qidong Cao,Zhuo Zhao, et al. Biogenesis, features, functions, and disease relationships of a specific Circular RNA: CDR1as[J]. Aging and disease, 10.14336/AD.2019.0920
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http://www.aginganddisease.org/EN/10.14336/AD.2019.0920     OR     http://www.aginganddisease.org/EN/Y0/V/I/0
Circular RNAmiRrefs
CDR1asmiR-78-12, 26, 29, 30, 53-65, 70
miR-6718-12
miR-129923
miR-876-5p24
miR-135a25
miR-139-3p, miR-471-5p, miR-3065-3p, miR-3132, miR-3134, miR-3145-3p, miR-3201, miR-3617-5p, miR-3637-3p, miR-4254, miR-4291, miR-4306, miR-6807-5p22
MiRs marked in yellow background may bind to CDR1as, from zhang's prediction by using TargetScan [22], but these have not been proved by experimental studies.
Table 1  miRs interacting with CDR1as.
Figure 1.  Model for biogenesis of CDR1as. In humans, CDR1 gene is located in the sex chromosome site: chrXq27.1 (140783260-140784558), gene ID: 1038 (www.ncbi.nlm.nih.gov/gene/1038), and CDR1 gene is encoded by a single exon without introns [32]. In humans, LINC00632 gene is located in the sex chromosome site: chrXq27.1 (140709759-140772677), gene ID: 286411, and encoded by five exons (www.ncbi.nlm.nih.gov/gene/?term=linc00632). Barrett discovered that the promoters of LINC00632 are responsible for driving CDR1as expression and that the CDR1as sequence is embedded in LINC00632 locus [31]. We speculate the pre-linear RNA of CDR1as is transcribed by the antisense strand of CDR1, which is followed by back-splicing of the 5' and 3' ends to form the circular RNA.
Figure 2.  Model for the network of CDR1as with related RNAs. CDR1as can act as a sponge for miR-7 and downregulate the inhibitory functions of miR-7 to target mRNAs, but not directly degrade miR-7 [18,19,20], and the same applies to miR-1299 [23], miR-876-5p [24], and miR-135a [25]. When CDR1as is lost, Cyrano is no longer inhibited by CDR1as and upregulated, and miR-7 is no longer sponged by CDR1as and more prone to be degraded by Cyrano [20]. Cyrano indirectly promotes the accumulation of CDR1as in brain tissue by promoting the destruction of miR-7 and further inhibiting miR-7-induced CDR1as degradation [21]. MiR-671 can directly slice CDR1as, while miR-7 can enhance miR-671-directed slicing of CDR1as [19,21] and also act to degrade CDR1as via at least one other unknown miR-7-dependent mechanism [21]. Solid arrow line represents promotion; dotted arrow line represents indirectly promotion; dotted T bars represent inhibition, but not slicing; solid T bars represent degradation; red solid T bar represents degradation, but the mechanism in unknown.
CDR1as sponge miRcancertarget genethe tumor's progressionRef
miR-7BCCCNE1promoting53
OSEGFR, CCNE1, PI3KCD,RAF1promoting54
LSCCproliferation indices ki-67, CCNE1, PIK3CDpromoting55
NSCLCproliferation indices Ki-67, EGFR, CCNE1, PIK3CDpromoting56
CRCEGFR, IGF-1Rpromoting58
PDACEGFR, STAT3promoting59
HCCEGFRpromoting60
CCNE1, PIK3CDpromoting61
PIK3CD, p70S6Kpromoting62
ESCCKLF-4, NF-κBpromoting63
HOXB13-mediated NF-κB/p65promoting64
miR-876-5pESCCMAGE-Apromoting24
miR-1299TNBCMMPspromoting23
miR-135abladder cancerp21Inhibiting25
Table 2  CDR1as in cancer.
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