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环状RNA mmu_circ_0000296通过miR-194-5p/Runx3/Sirt1轴对慢性脑缺血神经元凋亡的影响

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

作者信息

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

机构信息

Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, China.

Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang, China.

出版信息

Cell Death Discov. 2021 May 29;7(1):124. doi: 10.1038/s41420-021-00507-y.

DOI:10.1038/s41420-021-00507-y
PMID:34052838
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8164632/
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.

摘要

慢性脑缺血（CCI）是一种常见的病理紊乱，与多种疾病相关，如脑动脉硬化和血管性痴呆，可导致神经功能障碍。作为一种非编码RNA，环状RNA参与调节疾病的发生和发展，如缺血性脑损伤。在此，我们发现经CCI处理的HT22细胞和海马体中circ_0000296、Runx3、Sirt1表达较低，但miR-194-5p表达较高。circ_0000296、Runx3、Sirt1的过表达以及miR-194-5p的沉默显著抑制了CCI诱导的神经元凋亡。本研究表明，circ_0000296特异性结合miR-194-5p；miR-194-5p结合Runx3 mRNA的3'UTR区域；Runx3直接结合Sirt1的启动子区域，增强其转录活性。circ_0000296通过miR-194-5p减少了miR-194-5p对Runx3的负调控作用，促进了Runx3对Sirt1的转录作用，并抑制了CCI诱导的神经元凋亡。mmu_circ_0000296通过miR-194-5p/Runx3/Sirt1通路在调节CCI诱导的神经元凋亡中起重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff46/8164632/429646f500e2/41420_2021_507_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff46/8164632/bb9c3fd33541/41420_2021_507_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff46/8164632/e613ebc4c25b/41420_2021_507_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff46/8164632/7c3178159958/41420_2021_507_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff46/8164632/4a27faa56a70/41420_2021_507_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff46/8164632/f501a3611e5b/41420_2021_507_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff46/8164632/429646f500e2/41420_2021_507_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff46/8164632/bb9c3fd33541/41420_2021_507_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff46/8164632/e613ebc4c25b/41420_2021_507_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff46/8164632/7c3178159958/41420_2021_507_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff46/8164632/4a27faa56a70/41420_2021_507_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff46/8164632/f501a3611e5b/41420_2021_507_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff46/8164632/429646f500e2/41420_2021_507_Fig6_HTML.jpg

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