Long noncoding RNA antisense noncoding RNA in the INK4 locus inhibition alleviates airway remodeling in asthma through the regulation of the microRNA‐7‐5p/early growth response factor 3 axis

Abstract Asthma, a chronic inflammatory disease of the airways, clinically manifests as airway remodeling. The purpose of this study was to probe the potential role of long noncoding RNA (lncRNA) antisense noncoding RNA in the INK4 locus (lncRNA ANRIL) in the proliferation and migration of airway sm...

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Main Authors: Liyan Wang, Xueru Liu
Format: Article
Language:English
Published: Wiley 2023-04-01
Series:Immunity, Inflammation and Disease
Subjects:
Online Access:https://doi.org/10.1002/iid3.823
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author Liyan Wang
Xueru Liu
author_facet Liyan Wang
Xueru Liu
author_sort Liyan Wang
collection DOAJ
description Abstract Asthma, a chronic inflammatory disease of the airways, clinically manifests as airway remodeling. The purpose of this study was to probe the potential role of long noncoding RNA (lncRNA) antisense noncoding RNA in the INK4 locus (lncRNA ANRIL) in the proliferation and migration of airway smooth muscle cell (ASMC) and to explore its potential mechanisms in asthma. Serum samples were obtained from 30 healthy volunteers and 30 patients with asthma. Additionally, platelet‐derived growth factor‐BB (PDGF‐BB) was used to induce airway remodeling in ASMCs. The level of lncRNA ANRIL and microRNA (miR)‐7‐5p in serum samples were measured by quantitative reverse transcriptase polymerase chain reaction (qRT‐PCR). TargetScan predicted the binding site of miR‐7‐5p to early growth response factor 3 (EGR3) and validated the results using a dual‐luciferase reporter assay. 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2H‐tetrazolium bromide (MTT) and Transwell assays were used to detect cellular proliferation and migration, respectively. Subsequently, changes in proliferation‐ and migration‐related genes were verified using western blot analysis and qRT‐PCR. These results indicate that lncRNA ANRIL was upregulated in the serum and PDGF‐BB‐induced ASMCs of patients with asthma, whereas miR‐7‐5p expression was reduced. EGR3 was a direct target of miR‐7‐5p. LncRNA ANRIL silencing inhibited the proliferation or migration of ASMCs induced by PDGF‐BB through miR‐7‐5p upregulation. Mechanistic studies indicated that miR‐7‐5p inhibits the proliferation or migration of PDGF‐BB‐induced ASMCs by decreasing EGR3 expression. EGR3 upregulation reverses the role of miR‐7‐5p in airway remodeling. Thus, downregulation of lncRNA ANRIL inhibits airway remodeling through inhibiting the proliferation and migration of PDGF‐BB‐induced ASMCs by regulating miR‐7‐5p/EGR3 signaling.
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spelling doaj-art-e15e09a597a648e88f20a6cdf1ab45ab2025-08-20T02:16:50ZengWileyImmunity, Inflammation and Disease2050-45272023-04-01114n/an/a10.1002/iid3.823Long noncoding RNA antisense noncoding RNA in the INK4 locus inhibition alleviates airway remodeling in asthma through the regulation of the microRNA‐7‐5p/early growth response factor 3 axisLiyan Wang0Xueru Liu1Department of Pediatrics Wuhan Third Hospital Wuhan ChinaDepartment of Respiratory Medicine, Wuhan Children's Hospital, Tongji Medical College Huazhong University of Science & Technology Wuhan ChinaAbstract Asthma, a chronic inflammatory disease of the airways, clinically manifests as airway remodeling. The purpose of this study was to probe the potential role of long noncoding RNA (lncRNA) antisense noncoding RNA in the INK4 locus (lncRNA ANRIL) in the proliferation and migration of airway smooth muscle cell (ASMC) and to explore its potential mechanisms in asthma. Serum samples were obtained from 30 healthy volunteers and 30 patients with asthma. Additionally, platelet‐derived growth factor‐BB (PDGF‐BB) was used to induce airway remodeling in ASMCs. The level of lncRNA ANRIL and microRNA (miR)‐7‐5p in serum samples were measured by quantitative reverse transcriptase polymerase chain reaction (qRT‐PCR). TargetScan predicted the binding site of miR‐7‐5p to early growth response factor 3 (EGR3) and validated the results using a dual‐luciferase reporter assay. 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2H‐tetrazolium bromide (MTT) and Transwell assays were used to detect cellular proliferation and migration, respectively. Subsequently, changes in proliferation‐ and migration‐related genes were verified using western blot analysis and qRT‐PCR. These results indicate that lncRNA ANRIL was upregulated in the serum and PDGF‐BB‐induced ASMCs of patients with asthma, whereas miR‐7‐5p expression was reduced. EGR3 was a direct target of miR‐7‐5p. LncRNA ANRIL silencing inhibited the proliferation or migration of ASMCs induced by PDGF‐BB through miR‐7‐5p upregulation. Mechanistic studies indicated that miR‐7‐5p inhibits the proliferation or migration of PDGF‐BB‐induced ASMCs by decreasing EGR3 expression. EGR3 upregulation reverses the role of miR‐7‐5p in airway remodeling. Thus, downregulation of lncRNA ANRIL inhibits airway remodeling through inhibiting the proliferation and migration of PDGF‐BB‐induced ASMCs by regulating miR‐7‐5p/EGR3 signaling.https://doi.org/10.1002/iid3.823airway remodelingasthmalncRNA ANRILmigrationmiR‐7‐5pproliferation
spellingShingle Liyan Wang
Xueru Liu
Long noncoding RNA antisense noncoding RNA in the INK4 locus inhibition alleviates airway remodeling in asthma through the regulation of the microRNA‐7‐5p/early growth response factor 3 axis
Immunity, Inflammation and Disease
airway remodeling
asthma
lncRNA ANRIL
migration
miR‐7‐5p
proliferation
title Long noncoding RNA antisense noncoding RNA in the INK4 locus inhibition alleviates airway remodeling in asthma through the regulation of the microRNA‐7‐5p/early growth response factor 3 axis
title_full Long noncoding RNA antisense noncoding RNA in the INK4 locus inhibition alleviates airway remodeling in asthma through the regulation of the microRNA‐7‐5p/early growth response factor 3 axis
title_fullStr Long noncoding RNA antisense noncoding RNA in the INK4 locus inhibition alleviates airway remodeling in asthma through the regulation of the microRNA‐7‐5p/early growth response factor 3 axis
title_full_unstemmed Long noncoding RNA antisense noncoding RNA in the INK4 locus inhibition alleviates airway remodeling in asthma through the regulation of the microRNA‐7‐5p/early growth response factor 3 axis
title_short Long noncoding RNA antisense noncoding RNA in the INK4 locus inhibition alleviates airway remodeling in asthma through the regulation of the microRNA‐7‐5p/early growth response factor 3 axis
title_sort long noncoding rna antisense noncoding rna in the ink4 locus inhibition alleviates airway remodeling in asthma through the regulation of the microrna 7 5p early growth response factor 3 axis
topic airway remodeling
asthma
lncRNA ANRIL
migration
miR‐7‐5p
proliferation
url https://doi.org/10.1002/iid3.823
work_keys_str_mv AT liyanwang longnoncodingrnaantisensenoncodingrnaintheink4locusinhibitionalleviatesairwayremodelinginasthmathroughtheregulationofthemicrorna75pearlygrowthresponsefactor3axis
AT xueruliu longnoncodingrnaantisensenoncodingrnaintheink4locusinhibitionalleviatesairwayremodelinginasthmathroughtheregulationofthemicrorna75pearlygrowthresponsefactor3axis