MicroRNA let-7c-5p protects against cerebral ischemia injury via mechanisms involving the inhibition of microglia activation.
The present study was designed to reveal the potential role of let-7c-5p, a highly conserved miRNA in stroke. We found that the content of let-7c-5p was significantly decreased in the plasma of patients with ischemic stroke as well as in experimental animals. Moreover, we also observed a significant decrease of let-7c-5p in ipsilateral cortex and striatum in mice that were subjected to middle cerebral artery occlusion (MCAO) at 24h reperfusion. Overexpression of let-7c-5p via ICV injection decreased the infarction volume and attenuated the neurological deficits, and most interestingly, inhibited microglial activation. To further explore the mechanism, we checked let-7c-5p expression in BV2 cells and primary microglia in an OGD condition and in LPS-induced microglial activation. The results indicated that decreased let-7c-5p was evidenced in the activated microglia. Overexpression of let-7c-5p in BV2 cells remarkably inhibited the microglial activation. The inhibition of microglial activation by overexpression of let-7c-5p was also observed in mice with experimental stroke, which is in line with the decreased infarction volume and improved neurological deficits. We identified that let-7c-5p directly targeted to the 3'-untranslated region of the caspase 3 mRNA to reduce caspase 3 levels, which may underline the miRNA - modulated microglial activity. The present study revealed that suppression of microglia activation by let-7c-5p overexpression may be involved in the protection effects of ischemic damage. The mechanism may include the miRNA-mediated caspase 3 pathway.
Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215021, China.
Jingshu
J
Ni
Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215021, China.
Xiaoyu
X
Wang
Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215021, China.
Shuangshuang
S
Chen
The Second Affiliated Hospital of Soochow University, Soochow University, Suzhou, China.
Huihui
H
Liu
Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215021, China.
Yun
Y
Wang
Institute of Neuroscience, Soochow University, Suzhou, China; The Second Affiliated Hospital of Soochow University, Soochow University, Suzhou, China.
Xingshun
X
Xu
Institute of Neuroscience, Soochow University, Suzhou, China; The Second Affiliated Hospital of Soochow University, Soochow University, Suzhou, China.
Jian
J
Cheng
Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215021, China. Electronic address: jiajia@suda.edu.cn.
Jia
J
Jia
Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215021, China; College of Pharmaceutical Sciences and the Collaborative Innovation Center for Brain Science, Soochow University, Suzhou, China. Electronic address: zhenxuechu@suda.edu.cn.
Xuechu
X
Zhen
D020413:3' Untranslated Regions; D000368:Aged; D000818:Animals; D002545:Brain Ischemia / Q000097:blood*; D053148:Caspase 3 / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D004195:Disease Models, Animal; D004660:Encephalitis / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000008:administration & dosage / Q000097:blood* / Q000378:metabolism; D017628:Microglia / Q000378:metabolism*; D008875:Middle Aged; D020521:Stroke / Q000097:blood*
D020413:3' Untranslated Regions; D018836:Inflammation Mediators; D035683:MicroRNAs; D053148:Caspase 3
Ischemic stroke; Let-7c-5p; MicroRNA; Microglia