Effect of circular RNA, mmu_circ_0000296, on neuronal apoptosis in chronic cerebral ischaemia via the miR-194-5p/Runx3/Sirt1 axis

Keyu Huang,Yixue Xue,Di Wang,Bo Yu,Xuelei Ruan,Ping An,Jian Zheng,Chunqing Yang,Xiaobai Liu,Jie Liu,Dongfang Che

doi:10.1038/s41420-021-00507-y

Keyu Huang, Yixue Xue + Show 9 more

Open Access

https://doi.org/10.1038/s41420-021-00507-y

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Abstract

Chronic cerebral ischaemia (CCI) is a common pathological disorder, which is associated with various diseases, such as cerebral arteriosclerosis and vascular dementia, resulting in neurological dysfunction. As a type of non-coding RNA, circular RNA is involved in regulating the occurrence and development of diseases, such as ischaemic brain injury. Here, we found that HT22 cells and hippocampus treated with CCI had low expression of circ_0000296, Runx3, Sirt1, but high expression of miR-194-5p. Overexpression of circ_0000296, Runx3, Sirt1, and silenced miR-194-5p significantly inhibited neuronal apoptosis induced by CCI. This study demonstrated that circ_0000296 specifically bound to miR-194-5p; miR-194-5p bound to the 3′UTR region of Runx3 mRNA; Runx3 directly bound to the promoter region of Sirt1, enhancing its transcriptional activity. Overexpression of circ_0000296 by miR-194-5p reduced the negative regulatory effect of miR-194-5p on Runx3, promoted the transcriptional effect of Runx3 on Sirt1, and inhibited neuronal apoptosis induced by CCI. mmu_circ_0000296 plays an important role in regulating neuronal apoptosis induced by CCI through miR-194-5p/Runx3/Sirt1 pathway.

Highlights

Chronic cerebral ischaemia (CCI) is a progressive neurodegenerative process caused by long-term insufficient cerebral blood perfusion
The expression level of miR-194-5p in both normal and oxygen-glucose-deprived HT22 cells was evaluated, and the results showed that miR-194-5p expression in the oxygen-glucose-deprived group was significantly increased (Fig. 1d, P < 0.05). miR-194-5poverexpressing and miR-194-5p-silenced HT22 cells were oxygen-glucose deprived for 48 h to further study the effect of miR-194-5p on neuronal apoptosis induced by CCI
When we further explored the effect of co-transfection of miR-194-5p and Runx[3] on neuronal apoptosis induced by CCI, we found that apoptosis rate in the miR-194-5p + Runx3-(non3′-UTR) group decreased significantly compared with that in the miR-194-5p + Runx[3] group (Fig. 5b, P < 0.05), but compared with the miR-194-5p + Runx3-non-targeting sequence (NC) group, the apoptosis level in the miR-194-5p + Runx3-(non3′UTR) group decreased more drastically (Fig. 5b, P < 0.05)

Summary

Introduction

Chronic cerebral ischaemia (CCI) is a progressive neurodegenerative process caused by long-term insufficient cerebral blood perfusion. It is one of the main risk factors of some neurodegenerative diseases, such as vascular dementia (VD) and Alzheimer’s (AD)[1,2]. In the 2-VO model, cerebral blood flow decreases sharply in the early stage of ischaemia and is gradually recovered in the middle and late stages. This process is inconsistent with the hemodynamic changes in patients with CCI7. Compared with 2-VO and other models, the AC model simulates the changes in clinical haemodynamics of patients with CCI better[9]

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