LncRNA NEAT1: A novel regulator associated with the inflammatory response in acute respiratory distress syndrome

Shanhui Ge; Jiaxin Hu; Shijuan Gao; Jianwei Ren; Guangfa Zhu

doi:10.1016/j.gene.2023.147582

LncRNA NEAT1: A novel regulator associated with the inflammatory response in acute respiratory distress syndrome

Gene. 2023 Aug 20:878:147582. doi: 10.1016/j.gene.2023.147582. Epub 2023 Jun 21.

Authors

Shanhui Ge¹, Jiaxin Hu¹, Shijuan Gao², Jianwei Ren¹, Guangfa Zhu³

Affiliations

¹ Department of Respiratory and Critical Care Medicine, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
² Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, China.
³ Department of Respiratory and Critical Care Medicine, Beijing Anzhen Hospital, Capital Medical University, Beijing, China. Electronic address: guangfa_zhu@ccmu.edu.cn.

PMID: 37353041
DOI: 10.1016/j.gene.2023.147582

Abstract

Background: Acute respiratory distress syndrome (ARDS) is a life-threatening condition with an unfavorable prognosis. As the pathogenesis of ARDS remains unclear, we aimed to identify the core genes associated with ARDS and the mechanisms by which competing endogenous RNAs (ceRNAs) regulate the disease's progression.

Methods: Three mRNA microarray datasets (GSE17355, GSE48787, and GSE130936), derived from the Gene Expression Omnibus (GEO) database, were selected. Common differentially expressed genes (DEGs) related to acute lung injury (ALI) were identified and subjected to enrichment analysis. Then, hub genes were figured out through the protein-protein interaction (PPI) network and functional analysis, and targeted miRNAs and lncRNAs were predicted. Finally, the ceRNA networks associated with ALI were constructed and validated experimentally.

Results: A total of 155 upregulated and 93 downregulated DEGs were identified in the three datasets. The TNF signaling pathway and IL-17 signaling pathway were the most enriched pathways. Then, eleven DEGs enriched in the IL-17 signaling pathway were selected as the hub genes. Three miRNAs (mmu-mir-155-5p, mmu-mir-21a-5p, and mmu-mir-122-5p), which were located in the lung tissue and predicted to bind the hub genes at the same time, and two lncRNAs (Neat1 and Tug1), which have binding sites for the aforementioned miRNAs, were filtered. With qPCR verification, we identified a ceRNA network composed of NEAT1, miR-21-5p, MMP9, and CXCL5. NEAT1 knockdown promoted the migration and reduced the expression of pro-inflammatory factor and reactive oxygen species (ROS) in lung epithelial cells. We eventually confirmed that NEAT1/miR-21-5p/CXCL5/MMP9 played a pivotal role in regulating the inflammatory response in ALI.

Conclusion: The IL-17 signaling pathway is of great importance in the pathogenesis of ARDS. NEAT1/miR-21-5p is involved in the inflammation of ALI by regulating CXCL5 and MMP9.

Keywords: Acute respiratory distress syndrome; Bioinformatics analysis; IL-17 signaling pathway; Inflammation.

MeSH terms

Gene Regulatory Networks
Humans
Interleukin-17 / genetics
Matrix Metalloproteinase 9 / genetics
MicroRNAs* / genetics
MicroRNAs* / metabolism
RNA, Long Noncoding* / genetics
RNA, Long Noncoding* / metabolism
Respiratory Distress Syndrome* / genetics

Substances

RNA, Long Noncoding
Matrix Metalloproteinase 9
Interleukin-17
MicroRNAs