Oncotarget

Research Papers:

MicroRNA-27b inhibition promotes Nrf2/ARE pathway activation and alleviates intracerebral hemorrhage-induced brain injury

Wenzhe Xu, Feng Li, Zhiguo Liu, Zhenkuan Xu, Bin Sun, Jingwei Cao and Yuguang Liu _

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Oncotarget. 2017; 8:70669-70684. https://doi.org/10.18632/oncotarget.19974

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Abstract

Wenzhe Xu1, Feng Li1, Zhiguo Liu2, Zhenkuan Xu1, Bin Sun1, Jingwei Cao1 and Yuguang Liu1

1Department of Neurosurgery, Qilu Hospital and Brain Science Research Institute of Shandong University, Jinan 250012, P.R. China

2Department of Neurosurgery, People’s Hospital of Zhangqiu, Jinan 250200, P.R. China

Correspondence to:

Yuguang Liu, email: [email protected]

Feng Li, email: [email protected]

Keywords: intracerebral hemorrhage, microRNA-27b, Nrf2, oxidative stress, neuroinflammation

Received: December 27, 2016    Accepted: July 18, 2017    Published: August 07, 2017

ABSTRACT

Oxidative stress and neuroinflammation are the key factors leading to secondary brain injury after intracerebral hemorrhage (ICH). We investigated the effects of miR-27b, an oxidative stress-responsive microRNA, on ICH-induced brain injury in rats. The ICH model was induced by intracerebral injection of collagenase. Following ICH, miR-27b expression in the striatum was reduced, whereas expression of Nrf2 mRNA and protein was increased. In PC12 cells, overexpression of miR-27b reduced expression of Nrf2, Hmox1, Sod1 and Nqo1, while miR-27b inhibition had the opposite effects. Dual luciferase reporter assays showed that Nrf2 mRNA was a direct target of miR-27b. Intracerebroventricular injection of miR-27b antagomir and transfection of miR-27b inhibitor inhibited endogenous miR-27b in rats and PC12 cells, respectively. MiR-27b antagomir promoted activation of the ICH-induced Nrf2/ARE pathway and reduced the lipid peroxidation, neuroinflammation, cell death and neurological deficits otherwise seen after ICH. In PC12 cells, the miR-27b inhibitor diminished iron-induced oxidative stress, inflammation and apoptosis, and those effects were blocked by Nrf2 knockdown. These results demonstrate that miR-27b inhibition alleviates ICH-induced brain injury, which may be explained in part by its regulation on the Nrf2/ARE pathway.


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