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

// Wenzhe Xu 1 , Feng Li 1 , Zhiguo Liu 2 , Zhenkuan Xu 1 , Bin Sun 1 , Jingwei Cao 1 and Yuguang Liu 1 1 Department of Neurosurgery, Qilu Hospital and Brain Science Research Institute of Shandong University, Jinan 250012, P.R. China 2 Department of Neurosurgery, People’s Hospital of Zhangqiu, Jinan 250200, P.R. China Correspondence to: Yuguang Liu, email: docliuyuguang@126.com Feng Li, email: doclifeng@126.com 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.