Research Paper|Volume 12, Issue 4|pp 3156—3174

LncRNA MEG3 targeting miR-424-5p via MAPK signaling pathway mediates neuronal apoptosis in ischemic stroke

Yanxiao Xiang^1,^2,³, Yayun Zhang⁴, Yanni Xia⁵, Hua Zhao⁴, Anchang Liu¹, Yuguo Chen^2,^3,^6,^7,⁸

¹Department of Pharmacy, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China
²School of Medicine, Shandong University, Jinan 250100, Shandong, China
³Department of Emergency Medicine and Chest Pain Center, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China
⁴Department of Orthopedics, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China
⁵Department of Operating Room, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China
⁶Clinical Research Center for Emergency and Critical Care Medicine of Shandong Province, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China
⁷Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation of Shandong Province, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China
⁸The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China

Received: January 21, 2019Accepted: January 12, 2020Published: February 16, 2020

Copyright © 2020 Xiang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Emerging evidence suggests that long non-coding RNAs (lncRNAs) are significant regulators in the pathological process of ischemic stroke (IS). However, little is known about lncRNAs and their roles in IS. In this study, we aimed to screen out differentially expressed lncRNAs and revealed the underlying mechanisms in IS. The results of bioinformatic analysis showed that lncRNA MEG3 and Sema3A were over-expressed in IS samples, while miR-424-5p was lower-expressed. Correlation between MEG3/miR-424-5p, and miR-424-5p/Sema3A were predicted with miRanda and TargetScan, and verified by dual luciferase assay. Inhibition of MEG3 remarkably increased the expression of miR-424-5p and decreased the expression of Sema3A, which also led to in an increased cell viability and decreased cellular apoptosis in oxygen-glucose deprivation and reoxygenation (OGD/R) model, as well as an activated MAPK signaling pathways. Consistently, MEG3 was upregulated in MCAO mice, knockdown of MEG3 reduced the infarct volume and improved neurobehavioral outcomes in rats following MCAO. In conclusion, it was demonstrated that MEG3 accelerated the process of IS by suppressing miR-424-5p, which targeted Sema3A and the activated MAPK pathway. These results might provide useful information for exploring the potential therapeutic targets in IS.