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MicroRNA-365 Knockdown Prevents Ischemic Neuronal Injury by Activating Oxidation Resistance 1-Mediated Antioxidant Signals

  • Jia-Lin Mo
  • Zhi-Guang Pan
  • Xiao Chen
  • Yu Lei
  • Ling-Ling Lv
  • Cheng Qian
  • Feng-Yan SunEmail author
Original Article
  • 32 Downloads

Abstract

MicroRNA-365 (miR-365) is upregulated in the ischemic brain and is involved in oxidative damage in the diabetic rat. However, it is unclear whether miR-365 regulates oxidative stress (OS)-mediated neuronal damage after ischemia. Here, we used a transient middle cerebral artery occlusion model in rats and the hydrogen peroxide-induced OS model in primary cultured neurons to assess the roles of miR-365 in neuronal damage. We found that miR-365 exacerbated ischemic brain injury and OS-induced neuronal damage and was associated with a reduced expression of OXR1 (Oxidation Resistance 1). In contrast, miR-365 antagomir alleviated both the brain injury and OXR1 reduction. Luciferase assays indicated that miR-365 inhibited OXR1 expression by directly targeting the 3′-untranslated region of Oxr1. Furthermore, knockdown of OXR1 abolished the neuroprotective and antioxidant effects of the miR-365 antagomir. Our results suggest that miR-365 upregulation increases oxidative injury by inhibiting OXR1 expression, while its downregulation protects neurons from oxidative death by enhancing OXR1-mediated antioxidant signals.

Keywords

MicroRNA Ischemic stroke Neuronal damage Oxidative stress Neuroprotection 

Notes

Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (81030020, 81571197, and 81771268) and the National Education Program of China (J0730860).

Conflict of interest

The authors claim that there are no conflicts of interest.

Supplementary material

12264_2019_371_MOESM1_ESM.pdf (44 kb)
Supplementary material 1 (PDF 43 kb)

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Copyright information

© Shanghai Institutes for Biological Sciences, CAS 2019

Authors and Affiliations

  • Jia-Lin Mo
    • 1
    • 3
  • Zhi-Guang Pan
    • 2
    • 3
  • Xiao Chen
    • 1
    • 3
  • Yu Lei
    • 1
    • 3
  • Ling-Ling Lv
    • 1
    • 3
  • Cheng Qian
    • 1
    • 3
  • Feng-Yan Sun
    • 1
    • 2
    • 3
    • 4
    Email author
  1. 1.Department of Neurobiology and Institute for Basic Research on Aging and Medicine, School of Basic Medical SciencesFudan UniversityShanghaiChina
  2. 2.Department of Neurosurgery, National Clinical Research Center for Aging and Medicine, Huashan Hospital, Shanghai Medical CollegeFudan UniversityShanghaiChina
  3. 3.State Key Laboratory of Medical Neurobiology, School of Basic Medical SciencesFudan UniversityShanghaiChina
  4. 4.Shanghai Key Laboratory of Clinical Geriatric Medicine, Research Center on Aging and Medicine, Shanghai Medical CollegeFudan UniversityShanghaiChina

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