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circNup188/miR-760–3p/Map3k8 axis regulates inflammation in cerebral ischemia

生物 炎症 免疫印迹 缺血 信号转导 MAPK/ERK通路 肿瘤坏死因子α 细胞凋亡 小RNA NF-κB 细胞生物学 癌症研究 免疫学 内科学 基因 医学 遗传学
作者
Hui Zhang,Jian Deng,Kangling Huang,Yibo He,Zhili Cai,Yitao He
出处
期刊:Molecular and Cellular Probes [Elsevier]
卷期号:64: 101830-101830 被引量:15
标识
DOI:10.1016/j.mcp.2022.101830
摘要

Cerebral ischemia is a serious acute disease with high mortality and disability rates. circRNAs are associated with cerebral ischemia inflammation and can be used as therapeutic targets. We aimed to investigate circNup188/miR-760-3p/Map3k8 role in inflammation during cerebral ischemia.According to the sequencing results of previously published, signaling pathways and circRNAs related to inflammation were screened and looped for verification. In vitro OGD/R cell model was constructed to detect OGD/R effects on PC12 cell viability, apoptosis, inflammatory cytokines TNF-α, IL-1β and IL-6. qRT-PCR assessed circRNAs, circNup188 bound miRNAs, and four mRNAs associated with inflammation and brain diseases expressions. p65 and IkB-α and their phosphorylated proteins in NF-κB pathway and Map3k8 expressions were assessed by Western blot.KEGG analysis revealed MAPK and NF-kappaB signaling pathways played a vital role in it, and were classic inflammatory pathways. circNup188, circU2, and circCnot2 were verified to be the loop structure. circNup188 might play an essential role in OGD/R cell model. Regulating circNup188 expression could affect OGD/R cells function. In addition, miR-760-3p might play a vital role in OGD/R cell model. Moreover, circNup188 regulated cerebral ischemia by sponging miR-760-3p. miR-760-3p might be involved in inflammation in OGD/R cell model by regulating Map3k8 to activate the NF-κB pathway.circNup188 might up-regulate Map3k8 expression through sponging miR-760-3p and then activate NF-κB pathway, which was involved in cerebral ischemia development. This study provided a new target for cerebral ischemia treatment.

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