Long noncoding RNA IL6‐AS1 is highly expressed in chronic obstructive pulmonary disease and is associated with interleukin 6 by targeting miR‐149‐5p and early B‐cell factor 1

• Published in: Clinical and translational medicine 2021-07, Vol.11 (7), p.e479-n/a
• Main Authors: Yi, Erkang, Zhang, Jiahuan, Zheng, Mengning, Zhang, Yi, Liang, Chunxiao, Hao, Binwei, Hong, Wei, Lin, Biting, Pu, Jinding, Lin, Zhiwei, Huang, Peiyu, Li, Bing, Zhou, Yumin, Ran, Pixin
• Format: Article
• Language: English
• Subjects: Antagomirs - metabolism; Chronic obstructive pulmonary disease; Clinical medicine; Cytokines; Cytokines - metabolism; Cytoplasm - metabolism; early B‐cell factor 1; Experiments; Fibroblasts; Fibroblasts - cytology; Fibroblasts - metabolism; Genes; Histones - metabolism; hsa‐miR‐149‐5p; Humans; Hybridization; IL6‐AS1; IL‐6; Inflammation; Interleukin-6 - chemistry; Interleukin-6 - genetics; Interleukin-6 - metabolism; long noncoding RNA; Methylation; MicroRNAs; MicroRNAs - antagonists & inhibitors; MicroRNAs - genetics; MicroRNAs - metabolism; Promoter Regions, Genetic; Protein Binding; Proteins; Pulmonary Disease, Chronic Obstructive - genetics; Pulmonary Disease, Chronic Obstructive - pathology; Reagents; RNA Interference; RNA, Long Noncoding - antagonists & inhibitors; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; RNA, Small Interfering - metabolism; Smooth muscle; Trans-Activators - chemistry; Trans-Activators - metabolism
• ISSN: 2001-1326; 2001-1326
• DOI: 10.1002/ctm2.479

Chronic obstructive pulmonary disease is a complex condition with multiple etiologies, including inflammation. We identified a novel long noncoding RNA (lncRNA), interleukin 6 antisense RNA 1 (IL6‐AS1), which is upregulated in this disease and is associated with airway inflammation. We found that IL6‐AS1 promotes the expression of inflammatory factors, especially interleukin (IL) 6. Mechanistically, cytoplasmic IL6‐AS1 acts as an endogenous sponge by competitively binding to the microRNA miR‐149‐5p to stabilize IL‐6 mRNA. Nuclear IL6‐AS1 promotes IL‐6 transcription by recruiting early B‐cell factor 1 to the IL‐6 promoter, which increases the methylation of the H3K4 histone and acetylation of the H3K27 histone. We propose a model of lncRNA expression in both the nucleus and cytoplasm that exerts similar effects through differing mechanisms, and IL6‐AS1 probably increases inflammation via multiple pathways. The study provides the evidence that a novel lncRNA IL6‐AS1 is highly expressed in COPD and is associated with inflammation. IL6‐AS1 acts as the competitive endogenous RNA (ceRNA) to competitively bind to hsa‐miR‐149‐5p to regulate IL‐6 expression. IL6‐AS1 acts as a guide to promote the gene expression via recruiting EBF1 to the region of the IL‐6 promoter.