Functional predication of differentially expressed circRNAs/lncRNAs in the prefrontal cortex of Nrf2-knockout mice

In the central nervous system, nuclear factor erythroid-2-related factor 2 (Nrf2) protects neurons from oxidant injury, thereby ameliorating neurodegeneration. We explored the key circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) involved in Nrf2-induced neuroprotection. We used microarrays to examine the circRNAs (DEcircRNAs), lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) differentially expressed between Nrf2 (+/+) and Nrf2 (-/-) mice and identified DEcircRNA/DElncRNA-miRNA-DEmRNA interaction networks. In total, 197 DEcircRNAs, 685 DElncRNAs and 356 DEmRNAs were identified in prefrontal cortical tissues from Nrf2 (-/-) mice. The expression patterns of selected DEcircRNAs (except for mmu_circ_0003404) and DElncRNAs in qRT-PCR analyses were generally consistent with the microarray analysis results. Functional annotation of the DEmRNAs in the DEcircRNA/DElncRNA-miRNA-DEmRNA networks indicated that five non-coding RNAs (mmu_circ_0000233, ENSMUST00000204847, NONMMUT024778, NONMMUT132160 and NONMMUT132168) may contribute to Nrf2 activity, with the help of mmu_circ_0015035 and NONMMUT127961. The results also revealed that four non-coding RNAs (cicRNA.20127, mmu_circ_0012936, ENSMUST00000194077 and NONMMUT109267) may influence glutathione metabolism. Additionally, 44 DEcircRNAs and 7 DElncRNAs were found to possess coding potential. These findings provide clues to the molecular pathways through which Nrf2 protects neurons.