Research Paper Volume 13, Issue 6 pp 8797—8816

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

Yan-Jing Gao1, , Run-Jiao Zhang1, , Qing Liu1, , Shao-Guang Sun2, , Mao-Yang Qi3, , Yue Wang3, , Dan-Dan Geng1, , Lei Wang1, ,

  • 1 Department of Human Anatomy, Institute of Medicine and Health, Hebei Medical University, Shijiazhuang 050017, Hebei, China
  • 2 Department of Biochemistry and Molecular Biology, Hebei Medical University, Shijiazhuang 050017, Hebei, China
  • 3 School of Basic Medicine, Hebei Medical University, Shijiazhuang 050017, Hebei, China

Received: September 21, 2020       Accepted: February 1, 2021       Published: March 10, 2021
How to Cite

Copyright: © 2021 Gao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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.


Nrf2/NFE2L2: nuclear factor erythroid-2-related factor 2; CNC: cap ‘n’collar; ncRNA: non-coding RNA; circRNA: circular RNA; lncRNA: long non-coding RNA; miRNA: microRNA; ceRNA: competitive endogenous RNA; DEcircRNAs: differentially expressed circRNAs; DElncRNAs: differentially expressed lncRNAs; DEmRNAs: differentially expressed mRNAs; FC: fold change; PCR: polymerase chain reaction; MRE: miRNA response element; ALS: Amyotrophic lateral sclerosis; GSTs: glutathione S-transferases.