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

INTRODUCTION

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.