Overexpression of MALAT1 Relates to Lung Injury through Sponging miR-425 and Promoting Cell Apoptosis during ARDS.

Lu Wang,Lan Yao,Rui Zhang,Jiao Liu,Wenjie Xie,Bin Xu,Guang Li

doi:10.1155/2019/1871394

Abstract

Background Acute respiratory distress syndrome (ARDS) is a severe form of acute lung injury during which severe inflammatory responses induce cell apoptosis, necrosis, and fibrosis. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a multiple function long noncoding RNA that was found overexpressed during acute lung injury. However, the roles of MALAT1 in ARDS patients are still unknown. Methods Total RNA was extracted from the plasma, plasma exosome, and peripheral blood mononuclear cells (PBMCs) from 65 ARDS patients and 36 healthy controls. The MALAT1 and six candidate miRNAs levels were detected by qRT-PCR. The interaction between MALAT1 and miR-425 was predicted using a bioinformatics tool and verified by dual luciferase assay. Exosomes from ARDS patients were cultured with A549 and HFL-1 cells to confirm the delivery of miR-425 by exosomes. Cell apoptosis and viability were determined by flow cytometry and MTT assay. Results We found MALAT1 was significantly increased in the ARDS patients' plasma and PBMCs. The MALAT1 level in PBMCs was negatively correlated with exosomal miR-425 level. MALAT1 interacted with miR-425 and protected phosphatase and tensin homolog (PTEN) expression in A549 and HFL-1 cells. Exosomes from ARDS patients delivered less miR-425 into A549 and HFL-1 cells and induced cell apoptosis via upregulating PTEN. Conclusion This study identified increased MALAT1 and decreased miR-425 in ARDS patients and unveiled their roles during the pathogenesis of ARDS.

Highlights

Acute respiratory distress syndrome (ARDS) is a severe form of acute lung injury that occurs in critically ill or wounded patients which is characterized by widespread inflammation in the lungs and reduced oxygen uptake [1, 2]
To understand the roles of Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in ARDS, the MALAT1 level in plasma, peripheral blood mononuclear cells (PBMCs), and plasma exosomes was quantified by RT-PCR
We found the MALAT1 level was significantly increased in the plasma and PBMCs from ARDS patients (Figure 1(a))

Summary

Introduction

Acute respiratory distress syndrome (ARDS) is a severe form of acute lung injury that occurs in critically ill or wounded patients which is characterized by widespread inflammation in the lungs and reduced oxygen uptake [1, 2]. During ARDS processes, severe inflammatory responses induce cell apoptosis, necrosis, and fibrotic agents releasing, which contribute to the pathogenesis of the lungs [3]. Acute respiratory distress syndrome (ARDS) is a severe form of acute lung injury during which severe inflammatory responses induce cell apoptosis, necrosis, and fibrosis. The roles of MALAT1 in ARDS patients are still unknown. Exosomes from ARDS patients were cultured with A549 and HFL-1 cells to confirm the delivery of miR-425 by exosomes. MALAT1 interacted with miR-425 and protected phosphatase and tensin homolog (PTEN) expression in A549 and HFL-1 cells. Exosomes from ARDS patients delivered less miR-425 into A549 and HFL-1 cells and induced cell apoptosis via upregulating PTEN. Is study identified increased MALAT1 and decreased miR-425 in ARDS patients and unveiled their roles during the pathogenesis of ARDS Conclusion. is study identified increased MALAT1 and decreased miR-425 in ARDS patients and unveiled their roles during the pathogenesis of ARDS

Methods

Results

Conclusion