Melatonin Promotes Neuroprotection of H2O2-induced Neural Stem Cells via lncRNA MEG3/miRNA-27a-3p/MAP2K4 axis

Yuyong Chen; Lei He; Mao Pang; Zekai Ke; Xiaozuo Zheng; Feng Feng; Bu Yang; Nanxiang Wang; Bin Liu; Tao Wu; Tao Shu

doi:10.1016/j.neuroscience.2020.06.026

Melatonin Promotes Neuroprotection of H₂O₂-induced Neural Stem Cells via lncRNA MEG3/miRNA-27a-3p/MAP2K4 axis

Neuroscience. 2020 Oct 15:446:69-79. doi: 10.1016/j.neuroscience.2020.06.026. Epub 2020 Jun 26.

Authors

Yuyong Chen¹, Lei He¹, Mao Pang¹, Zekai Ke², Xiaozuo Zheng³, Feng Feng¹, Bu Yang¹, Nanxiang Wang¹, Bin Liu⁴, Tao Wu⁵, Tao Shu⁶

Affiliations

¹ Department of Spine Surgery, The 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China; Guangdong Provincial Center for Quality Control of Minimally Invasive Spine Surgery, Guangzhou, Guangdong 510630, China; Guangdong Provincial Center for Engineering and Technology Research of Minimally Invasive Spine Surgery, Guangzhou, Guangdong 510630, China.
² Department of Orthopaedic Surgery, Shenzhen University General Hospital, Shenzhen, Guangdong 518055, China.
³ Department of Orthopaedic Surgery, The 3rd Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, China.
⁴ Department of Spine Surgery, The 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China; Guangdong Provincial Center for Quality Control of Minimally Invasive Spine Surgery, Guangzhou, Guangdong 510630, China; Guangdong Provincial Center for Engineering and Technology Research of Minimally Invasive Spine Surgery, Guangzhou, Guangdong 510630, China. Electronic address: johnliu2001@126.com.
⁵ Armyman Ward of the First Surgical Department, Guangdong Provincial Corps Hospital of Chinese People's Armed Police Forces, Guangzhou Medical University, Guangzhou, Guangdong 510000, China. Electronic address: doctorwutao@163.com.
⁶ Department of Spine Surgery, The 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China; Guangdong Provincial Center for Quality Control of Minimally Invasive Spine Surgery, Guangzhou, Guangdong 510630, China; Guangdong Provincial Center for Engineering and Technology Research of Minimally Invasive Spine Surgery, Guangzhou, Guangdong 510630, China. Electronic address: shutao2019@126.com.

PMID: 32599124
DOI: 10.1016/j.neuroscience.2020.06.026

Abstract

Melatonin is crucial for protecting neural stem cells (NSCs) from reactive oxygen species (ROS). However, the mechanism underlying these processes is unclear. In this study, we first investigated the significantly upregulated lncRNA MEG3 biomarker in the H₂O₂-induced NSCs and control groups. Melatonin inhibited the expression of MEG3 by methylation. MEG3 overexpression reversed the positive effects of melatonin on NSCs against H₂O₂. Furthermore, MEG3 reduced the expression levels of its targeted miRNA-27a-3p, which could be considered a neuroprotective effect. In addition, the elevated miRNA-27a-3p decreased JNK phosphorylation by targeting MAP2K4. Overexpression of MAP2K4 suppressed the neuroprotective effects of miRNA-27a-3p. Therefore, melatonin appeared to protect NSCs from H₂O₂-induced ROS by modification of the MEG3/miRNA-27a-3p/MAP2K4 axis.

Keywords: MAP2K4; MEG3; melatonin; miRNA-27a-3p; neural stem cells; reactive oxygen species.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Hydrogen Peroxide / toxicity
Melatonin* / pharmacology
MicroRNAs* / genetics
Neural Stem Cells*
Neuroprotection
RNA, Long Noncoding* / genetics

Substances

MicroRNAs
RNA, Long Noncoding
Hydrogen Peroxide
Melatonin