Long non-coding RNA SNHG4 aggravates cigarette smoke-induced COPD by regulating miR-144-3p/EZH2 axis

Abstract Objective The purpose of this study was to explore the expression level of SNHG4 in patients with COPD and its diagnostic value in COPD, to probe the biological function of SNHG4 in COPD at the cellular level, and to reveal the interaction between SNHG4 and miR-144-3p/EZH2 axis. Methods The...

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Main Authors: Benyan Song, Yusi Chen
Format: Article
Language:English
Published: BMC 2023-12-01
Series:BMC Pulmonary Medicine
Subjects:
Online Access:https://doi.org/10.1186/s12890-023-02818-5
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author Benyan Song
Yusi Chen
author_facet Benyan Song
Yusi Chen
author_sort Benyan Song
collection DOAJ
description Abstract Objective The purpose of this study was to explore the expression level of SNHG4 in patients with COPD and its diagnostic value in COPD, to probe the biological function of SNHG4 in COPD at the cellular level, and to reveal the interaction between SNHG4 and miR-144-3p/EZH2 axis. Methods The serum levels of SNHG4, miR-144-3p and EZH2 in healthy people and patients with COPD were detected by RT-qPCR. The diagnostic value of SNHG4 in COPD was evaluated by ROC curve. Pearson method was chosen to estimate the correlation between SNHG4 and clinical indicators in patients with COPD. Cigarette smoke extract (CSE) was obtained, and Beas-2B cells were exposed with 2% CSE to establish an inflammatory cell model of COPD in vitro. MTT assay was used to detect cell viability, flow cytometry was used to evaluate cell apoptosis, and ELISA was performed to detect inflammatory cytokines. Dual-luciferase reporting assay was carried out to verify the targeting of lncRNA-miRNA or miRNA-mRNA. Results (1) The expression of SNHG4 is decreased in patients with COPD, and the expression level in acute exacerbation COPD was lower than that in stable COPD. SNHG4 demonstrated high diagnostic accuracy in distinguishing between stable and acute exacerbation COPD. (2) The expression of SNHG4 was decreased in CSE-induced Beas-2B cells, and overexpression of SNHG4 was beneficial to alleviate CSE-induced apoptosis and inflammation. (3) The expression of miR-144-3p is up-regulated in patients with COPD and CSE-induced Beas-2B cells. MiR-144-3p has a targeting relationship with SNHG4, which is negatively regulated by SNHG4. Overexpression of miR-144-3p could counteract the beneficial effects of increased SNHG4 on CSE-induced cells. (4) The expression of EZH2 is reduced in patients with COPD and CSE-induced Beas-2B cells. Bioinformatics analysis and luciferase reporter gene confirmed that EZH2 is the downstream target gene of miR-144-3p and is negatively regulated by miR-144-3p. Conclusion The expression of SNHG4 decreased in patients with COPD, and it may promote the progression of COPD by inhibiting the viability, promoting apoptosis and inflammatory response of bronchial epithelial cells via regulating the miR-144-3p/EZH2 axis.
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spelling doaj.art-fd719ef559a448e3884cb31435efc8332023-12-24T12:08:56ZengBMCBMC Pulmonary Medicine1471-24662023-12-0123111210.1186/s12890-023-02818-5Long non-coding RNA SNHG4 aggravates cigarette smoke-induced COPD by regulating miR-144-3p/EZH2 axisBenyan Song0Yusi Chen1Department of Pulmonary and Critical Care Medicine, Affiliated Hospital of Panzhihua UniversityDepartment of Pulmonary and Critical Care Medicine, Affiliated Hospital of Panzhihua UniversityAbstract Objective The purpose of this study was to explore the expression level of SNHG4 in patients with COPD and its diagnostic value in COPD, to probe the biological function of SNHG4 in COPD at the cellular level, and to reveal the interaction between SNHG4 and miR-144-3p/EZH2 axis. Methods The serum levels of SNHG4, miR-144-3p and EZH2 in healthy people and patients with COPD were detected by RT-qPCR. The diagnostic value of SNHG4 in COPD was evaluated by ROC curve. Pearson method was chosen to estimate the correlation between SNHG4 and clinical indicators in patients with COPD. Cigarette smoke extract (CSE) was obtained, and Beas-2B cells were exposed with 2% CSE to establish an inflammatory cell model of COPD in vitro. MTT assay was used to detect cell viability, flow cytometry was used to evaluate cell apoptosis, and ELISA was performed to detect inflammatory cytokines. Dual-luciferase reporting assay was carried out to verify the targeting of lncRNA-miRNA or miRNA-mRNA. Results (1) The expression of SNHG4 is decreased in patients with COPD, and the expression level in acute exacerbation COPD was lower than that in stable COPD. SNHG4 demonstrated high diagnostic accuracy in distinguishing between stable and acute exacerbation COPD. (2) The expression of SNHG4 was decreased in CSE-induced Beas-2B cells, and overexpression of SNHG4 was beneficial to alleviate CSE-induced apoptosis and inflammation. (3) The expression of miR-144-3p is up-regulated in patients with COPD and CSE-induced Beas-2B cells. MiR-144-3p has a targeting relationship with SNHG4, which is negatively regulated by SNHG4. Overexpression of miR-144-3p could counteract the beneficial effects of increased SNHG4 on CSE-induced cells. (4) The expression of EZH2 is reduced in patients with COPD and CSE-induced Beas-2B cells. Bioinformatics analysis and luciferase reporter gene confirmed that EZH2 is the downstream target gene of miR-144-3p and is negatively regulated by miR-144-3p. Conclusion The expression of SNHG4 decreased in patients with COPD, and it may promote the progression of COPD by inhibiting the viability, promoting apoptosis and inflammatory response of bronchial epithelial cells via regulating the miR-144-3p/EZH2 axis.https://doi.org/10.1186/s12890-023-02818-5Chronic Obstructive Pulmonary DiseaseSNHG4MiR-144-3pEZH2Inflammation
spellingShingle Benyan Song
Yusi Chen
Long non-coding RNA SNHG4 aggravates cigarette smoke-induced COPD by regulating miR-144-3p/EZH2 axis
BMC Pulmonary Medicine
Chronic Obstructive Pulmonary Disease
SNHG4
MiR-144-3p
EZH2
Inflammation
title Long non-coding RNA SNHG4 aggravates cigarette smoke-induced COPD by regulating miR-144-3p/EZH2 axis
title_full Long non-coding RNA SNHG4 aggravates cigarette smoke-induced COPD by regulating miR-144-3p/EZH2 axis
title_fullStr Long non-coding RNA SNHG4 aggravates cigarette smoke-induced COPD by regulating miR-144-3p/EZH2 axis
title_full_unstemmed Long non-coding RNA SNHG4 aggravates cigarette smoke-induced COPD by regulating miR-144-3p/EZH2 axis
title_short Long non-coding RNA SNHG4 aggravates cigarette smoke-induced COPD by regulating miR-144-3p/EZH2 axis
title_sort long non coding rna snhg4 aggravates cigarette smoke induced copd by regulating mir 144 3p ezh2 axis
topic Chronic Obstructive Pulmonary Disease
SNHG4
MiR-144-3p
EZH2
Inflammation
url https://doi.org/10.1186/s12890-023-02818-5
work_keys_str_mv AT benyansong longnoncodingrnasnhg4aggravatescigarettesmokeinducedcopdbyregulatingmir1443pezh2axis
AT yusichen longnoncodingrnasnhg4aggravatescigarettesmokeinducedcopdbyregulatingmir1443pezh2axis