miRNA-1283 Regulates the PERK/ATF4 Pathway in Vascular Injury by Targeting ATF4

作者：Ling He, Jing Yuan, Qingyun Xu, Ruixue Chen, Liguo Chen, Meixia Fang · 发表于：PLoS ONE · 年份：2016 · DOI：10.1371/journal.pone.0159171 · 被引用次数：34 · 研究领域：Endoplasmic Reticulum Stress and Disease、RNA regulation and disease、Autophagy in Disease and Therapy

BACKGROUND: In our previous study, we found significant differences in the mRNA and microRNA (miRNA) levels among hypertensive patients with different degrees of vascular endothelial cells damage. These differences were closely associated with endoplasmic reticulum stress (ERS)-related proteins. Moreover, compared to the control group, the expression of transcription factor activating factor 4 (ATF4) was also found to be significantly different in the hypertensive patients with different degrees of vascular endothelial cells damage groups. These results were confirmed using gene prediction software, which showed synergistic effects between ATF4 and miR-1283. ATF4 is a key molecule in ERS. Three ERS pathways exist:protein kinase RNA-like ER kinase (PERK), activating transcription factor 6 (ATF6) and inositol-requiring enzyme-1 (IRE-1)-induced apoptosis. The PERK pathway is the most important and also includes the phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) and ATF4. In this report, we studied the regulatory effects of miR-1283 and ATF4 on the PERK-eIF2α-ATF4 signaling pathway using human umbilical vein endothelial cells (HUVECs) and mice. METHODOLOGY/PRINCIPAL FINDINGS: We verified the relationship between miR-1283 and ATF4 using a luciferase activity assay and observed the regulatory effects of miR-1283 and ATF4 on the PERK-eIF2α-ATF4 signaling pathway in vivo and in vitro. CONCLUSIONS/SIGNIFICANCE: ATF4 is a target gene of miR-1283, which regulates...