MiR-203 Targets to the 3'-UTR of SLUG to Suppress Cerebral Infarction-Induced Endothelial Cell Growth and Motility.

Yunsong Li,Wei Bi,Tao Yuan,Bing Han,Yang Liu,Huanhuan Sun,Xiang Gao,Long Shi,Xueyan Li

doi:10.1155/2021/5597567

Abstract

Cerebral infarction is one of the leading causes of death worldwide, in which angiogenesis plays a critical role. On the other hand, accumulating evidence has demonstrated that microRNAs (miRNAs) function as key modulators in the formation and progression of cerebral infarction. However, the molecular mechanisms of miRNAs underlying cerebral infarction-associated angiogenesis remain unclear. In the present study, we indicated that the expression of miR-203 was significantly downregulated in serum samples derived from patients with cerebral infarction and in mice brain samples following middle cerebral artery occlusion (MCAO) compared with healthy controls. In vitro, the expression of miR-203 was obviously downregulated in hypoxia-induced human umbilical vein vascular endothelial cells (HUVECs). Functionally, ectopic expression of miR-203 drastically suppressed HUVEC proliferation, invasion, and migration. In addition, SLUG, a zinc finger transcriptional repressor, was identified as a direct target of miR-203 and was negatively correlated with miR-203 expression in MCAO mice and in hypoxia-induced HUVECs. Furthermore, overexpression of SLUG reversed the inhibitory effect of miR-203 on proliferation, invasion, and migration abilities of HUVECs. Taken together, our research provides a novel insight of the miR-203-SLUG axis into cerebral infarction-associated endothelial behaviors and may offer a powerful therapeutic target of cerebral ischemia.

Highlights

Cerebral infarction is one of the leading causes of death for people over 60 years old worldwide [1,2,3]
MiR-203 Expression Is Reversely Correlated with SLUG in Serum Samples Derived from Patients with Ischemic Infarction, Brain Tissues Derived from middle cerebral artery occlusion (MCAO) Mice, and HypoxiaInduced human umbilical vein vascular endothelial cells (HUVECs)
We examined miR-203 and SLUG expression in hypoxia-induced HUVECs. e results demonstrated that miR-203 was obviously downregulated in HUVECs with hypoxic treatment compared with normal cells (Figure 1(g)), while SLUG was upregulated (Figure 1(h) and 1(i)). ese findings indicate that downregulation of miR-203 and upregulation of SLUG may be attributed to ischemia

Summary

Introduction

Cerebral infarction is one of the leading causes of death for people over 60 years old worldwide [1,2,3]. Accumulating studies have demonstrated that a wide range of genes and signaling pathways are involved in cerebral ischemia, the precise molecular mechanisms remain not fully elucidated. Previous studies have proved that ischemic stroke can initiate angiogenesis to recover the oxygen and nutrient supply and facilitate functional recovery in damaged brain tissues [4,5,6,7]. The molecular mechanisms underlying cerebral infarction-related angiogenesis are not well documented. MiRNAs have been widely reported to be implicated in multiple physiological and pathological processes, including cell proliferation, apoptosis, tissue homeostasis, organ development, carcinogenesis, inflammation, and ischemic diseases. Cai et al have reported that miR-146b-3p regulates the development and progression of cerebral infarction with diabetes through RAF1/P38MAPK/COX-2 signaling pathway [11].

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