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

Abstract

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.

Theaflavin-3,3'-Digallate Protects Liver and Kidney Functions in Diabetic Rats by Up-Regulating Circ-ITCH and Nrf2 Signaling Pathway

“…Recent studies have shown that certain circ-RNAs can influence disease processes by regulating oxidative stress and modulating the Nrf2 pathway. Gao 29 et al found that the types and amounts of circ-RNAs in mouse prefrontal cortex were significantly different before and after Nrf2 knockdown, suggesting that circ-0000233, circ-0015035, and circ-0012936 may contribute to the effects of the Nrf2 pathway on cognitive function. In related reports on diabetes and its complications, circ-ITCH, circ-HIPK3, and circ-UBAP2 may regulate the Nrf2 pathway to influence oxidative damage.…”

“…Recent studies have shown that certain circ-RNAs can influence disease processes by regulating oxidative stress and modulating the Nrf2 pathway. Gao et al found that the types and amounts of circ-RNAs in mouse prefrontal cortex were significantly different before and after Nrf2 knockdown, suggesting that circ-0000233, circ-0015035, and circ-0012936 may contribute to the effects of the Nrf2 pathway on cognitive function. In related reports on diabetes and its complications, circ-ITCH, circ-HIPK3, and circ-UBAP2 may regulate the Nrf2 pathway to influence oxidative damage. ,, Among these, circ-ITCH would be used as a target for the remedy of diabetic kidney damage. , Circ-ITCH has also been mentioned several times in relation to liver damage. − Our investigation indicated that TFDG upregulates circ-ITCH, which performs an essential function in regulating the Nrf2 pathway to protect against diabetic liver and kidney injury.…”

Role of Non-coding RNAs in Axon Regeneration after Peripheral Nerve Injury

“…The length of circRNAs varies from 200-2000 nucleotides, with the majority having lengths of about 500 nucleotides, which are generally located in the cytoplasm. The direct ligation of the exonic downstream 5' donor site with the upstream 3' acceptor site results in a closed loop structure, which makes circRNAs resistant to degradation by exonuclease RNaseR and helps them maintain high stability and conserved sequence 43 . According to their origin, circRNAs may be composed of exons, introns and exon-intron structures (ElciRNA) 44 .…”

Response to comments on our article (Yin YL et al., Parasit Vectors, 10.1186/s13071-021-04739-w) by Yuqing Wang and colleagues

“…Due to the generally mild impact of Cryptosporidium infection on host cell gene transcription compared to other pathogens [9][10][11][12], to obtain as many differentially expressed genes as possible, we chose fold changes > 2 combined with P ≤ 0.05 as the threshold to preliminarily screen differentially expressed circRNAs in the microarray analysis in our article [3]. The criterion of P <0.05 or P ≤ 0.05 was also used by recent studies [13][14][15][16]. From the subsequent verification of the experimental results, circRNAs of interest obtained using the threshold of P ≤ 0.05 are stable and accurate.…”