Abstract TP279: lncRNA Cyrano mediates post-stroke degradation of microRNA miR-7

Transient focal ischemia rapidly disrupts the expression of various noncoding RNAs, including miRNAs, which regulate brain injury and recovery. Among these, miR-7, which is a pro-survival miRNA, is downregulated in the ischemic brain, leading to derepression of its target α-synuclein, which promotes neuronal death. In the brain, miR-7 levels are influenced by the circRNA CDR1as, which stabilizes miR-7, and lncRNA Cyrano, which facilitates its degradation. Following transient focal ischemia, CDR1as levels significantly decreased, while pri-miR-7 levels were unchanged, suggesting that mature miR-7 is reduced due to increased post-transcriptional degradation. Bioinformatics analysis revealed strong sequence complementarity between Cyrano and miR-7. Experimentally, Cyrano was upregulated in the ischemic brain and capable of binding and degrading free miR-7. Cyrano knockout mice showed increased cerebral miR-7 levels after ischemia, whereas miR-7 knockout didn’t affect Cyrano levels. Importantly, mice lacking Cyrano showed improved motor recovery and less brain damage after transient focal ischemia, likely due to reduced α-Synuclein levels. These findings reveal that noncoding RNA crosstalk regulates miRNA stability and function in the brain after stroke.