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.
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 . 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 . 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 , miR-876-5p , and miR-135a . 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 . 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 . 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 . 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 miR
the tumor's progression
EGFR, CCNE1, PI3KCD,RAF1
proliferation indices ki-67, CCNE1, PIK3CD
proliferation indices Ki-67, EGFR, CCNE1, PIK3CD
Table 2 CDR1as in cancer.
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