Abstract
Background
Extensive studies have revealed that long non-coding RNAs (lncRNAs) are associated
with sepsis-induced acute lung injury (ALI). This study focused on the function and
potential mechanisms of lncRNA zinc finger antisense 1 (ZFAS1) in a cell model of sepsis-induced ALI.
Methods
To induce sepsis-induced ALI in vitro and in vivo, mice were subjected to cecal ligation and puncture (CLP) operation, and human small
airway epithelial cells (HSAECs) were stimulated with lipopolysaccharide (LPS) (10
μg/mL). Relative expression of oxidative stress-responsive 1 (OXSR1), lncRNA ZFAS1, and microRNA (miR)-96-5p was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Relative
protein expression of Bax, Bcl-2, and OXSR1 was determined by western blotting. Moreover,
enzyme-linked immunosorbent assay was used to measure the levels of IL-6, IL-1β, and
TNF-α. A dual-luciferase reporter assay was conducted to test the targeting interplay
between ZFAS1/OXSR1 and miR-96-5p.
Results
Up-regulation of lncRNA ZFAS1 and OXSR1 and down-regulation of miR-96-5p was observed in lung tissues of CLP-induced mice and LPS-treated HSAECs. Decreased
ZFAS1 expression or increased miR-96-5p expression repressed inflammation and apoptosis and promoted cell viability in LPS-treated
HSAECs. The lncRNA ZFAS1 competitively binds to miR-96-5p and inversely modulates miR-96-5p expression. MiR-96-5p directly targets OXSR1 and inversely regulates OXSR1 expression. In addition, the protective effects of ZFAS1 knockdown on LPS-induced HSAECs were reversed by miR-96-5p inhibition or OXSR1 overexpression.
Conclusions
Down-regulation of lncRNA ZFAS1 attenuated LPS-induced ALI in HSAECs by regulating the miR-96-5p/OXSR1 axis.
Key Indexing Terms
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References
- Sepsis: a review of advances in management.Adv Ther. 2017; 34: 2393-2411
- Sepsis Guidelines.N Engl J Med. 2019; 380: 1369-1371
- Pathophysiology of sepsis.Anasthesiol Intensivmed Notfallmed Schmerzther. 2015; 50: 114-122
- Volatile anesthetic preconditioning attenuated sepsis induced lung inflammation.J Surg Res. 2012; 178: e17-e23
- Incidence and outcomes of acute lung injury.N Engl J Med. 2005; 353: 1685-1693
- Mortality in sepsis versus non-sepsis induced acute lung injury.Crit Care. 2009; 13: R150
- Sepsis: pathophysiology and clinical management.BMJ. 2016; 353: i1585
- Clinical epidemiology of acute lung injury and acute respiratory distress syndrome: incidence, diagnosis, and outcomes.Clin Chest Med. 2006; 27 (abstract vii): 549-557
- Sepsis: a roadmap for future research.Lancet Infect Dis. May 2015; 15: 581-614
- Lower tidal volume ventilation and plasma cytokine markers of inflammation in patients with acute lung injury.Crit Care Med. Jan 2005; 33 (1-6; discussion): 230-232
- The role of apoptosis in acute lung injury.Crit Care Med. Apr 2003; 31: S184-S188
- Identification and function of long non-coding RNA.Front Cell Neurosci. 2013; 7: 168
- Insights into the function of long noncoding RNAs in sepsis revealed by gene co-expression network analysis.Noncoding RNA. 2017; 3
- LncRNA TUG1 alleviates sepsis-induced acute lung injury by targeting miR-34b-5p/GAB1.BMC Pulm Med. 2020; 20: 49
- Depression of lncRNA NEAT1 antagonizes LPS-evoked acute injury and inflammatory response in alveolar epithelial cells via HMGB1-RAGE signaling.Mediators Inflamm. 2020; 20208019467
- SP1-induced ZFAS1 aggravates sepsis-induced cardiac dysfunction via miR-590-3p/NLRP3-mediated autophagy and pyroptosis.Arch Biochem Biophys. 2020; 695108611
- lncRNA ZFAS1 promotes lung fibroblast-to-myofibroblast transition and ferroptosis via functioning as a ceRNA through miR-150-5p/SLC38A1 axis.Aging (Albany NY). 2020; 12: 9085-9102
- Targeting noncoding RNAs in disease.J Clin Invest. Mar 1 2017; 127: 761-771
- LncRNA MALAT1 regulates sepsis-induced cardiac inflammation and dysfunction via interaction with miR-125b and p38 MAPK/NFkappaB.Int Immunopharmacol. 2018; 55: 69-76
- Down-regulation of LncRNA CRNDE aggravates kidney injury via increasing MiR-181a-5p in sepsis.Int Immunopharmacol. 2020; 79105933
- Identification of novel genes coding for small expressed RNAs.Science. 2001; 294: 853-858
- MicroRNAs: genomics, biogenesis, mechanism, and function.Cell. 2004; 116: 281-297
- MiR-539-5p alleviates sepsis-induced acute lung injury by targeting ROCK1.Folia Histochem Cytobiol. 2019; 57: 168-178
- High expression of miR-483-5p aggravates sepsis-induced acute lung injury.J Toxicol Sci. 2020; 45: 77-86
- miR-96-5p Suppresses the progression of nasopharyngeal carcinoma by targeting CDK1.Onco Targets Ther. 2020; 13: 7467-7477
- SIKIAT1/miR-96/FOXA1 axis regulates sepsis-induced kidney injury through induction of apoptosis.Inflamm Res. 2020; 69: 645-656
- MiR-96-5p alleviates inflammatory responses by targeting NAMPT and regulating the NF-kappaB pathway in neonatal sepsis.Biosci Rep. 31 2020; 40
- Nuclear factor-kappaB decoy oligodeoxynucleotides prevent acute lung injury in mice with cecal ligation and puncture-induced sepsis.Mol Pharmacol. 2005; 67: 1018-1025
- Sepsis modeling in mice: ligation length is a major severity factor in cecal ligation and puncture.Intensive Care Med Exp. 2016; 4: 22
- LncRNA THRIL aggravates sepsis-induced acute lung injury by regulating miR-424/ROCK2 axis.Mol Immunol. 2020; 126: 111-119
- Down-regulation of lncRNA CASC9 aggravates sepsis-induced acute lung injury by regulating miR-195-5p/PDK4 axis.Inflamm Res. 2020; 69: 559-568
- An official American Thoracic Society workshop report: features and measurements of experimental acute lung injury in animals.Am J Respir Cell Mol Biol. 2011; 44: 725-738
- Sepsis: current definition, pathophysiology, diagnosis, and management.Nutr Clin Pract. 2017; 32: 296-308
- Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy.Nat Rev Immunol. 2013; 13: 862-874
- Correlations of inflammation, oxidative stress and prognosis with expression of LncRNA H19 in rats with sepsis-evoked lung injury.Panminerva Med. 2020;
- MEG3-4 is a miRNA decoy that regulates IL-1beta abundance to initiate and then limit inflammation to prevent sepsis during lung infection.Sci Signal. 2018; 11
- Analyzing MiRNA-LncRNA Interactions.Methods Mol Biol. 2016; 1402: 271-286
- Upregulation of lncRNA ZFAS1 promotes lung adenocarcinoma progression by sponging miR-1271-5p and upregulating FRS2.Thorac Cancer. 2020; 11: 2178-2187
- Long noncoding RNA ZFAS1 acts as an oncogene by targeting miR-193a-3p in human non-small cell lung cancer.Eur Rev Med Pharmacol Sci. 2019; 23: 6516-6523
- microRNA functions.Annu Rev Cell Dev Biol. 2007; 23: 175-205
- Molecular cloning and characterization of OSR1 on human chromosome 2p24.Int J Mol Med. 2002; 10: 221-225
- MicroRNA-191-5p diminished sepsis-induced acute kidney injury through targeting oxidative stress responsive 1 in rat models.Biosci Rep. 2019; 39
Article info
Publication history
Published online: April 03, 2022
Accepted:
March 30,
2022
Received:
February 4,
2021
Identification
Copyright
© 2022 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.
