PMID- 37359246
OWN - NLM
STAT- Publisher
LR  - 20230928
IS  - 1738-642X (Print)
IS  - 2092-8467 (Electronic)
IS  - 1738-642X (Linking)
DP  - 2023 May 25
TI  - CircSLCO3A1 depletion ameliorates lipopolysaccharide-induced inflammation and 
      apoptosis of human pulmonary alveolar epithelial cells through the 
      miR-424-5p/HMGB3 pathway.
PG  - 1-12
LID - 10.1007/s13273-023-00341-6 [doi]
AB  - BACKGROUND: Recent studies have shown the pathogenesis of acute lung injury (ALI) 
      involves circular RNA (circRNA). However, there are no data on the role of 
      circSLCO3A1 in ALI and the underlying mechanism. OBJECTIVE: ALI-like cell injury 
      was induced by stimulating human pulmonary alveolar epithelial cells (HPAEpiCs) 
      using lipopolysaccharide (LPS). The expression of circSLCO3A1, miR-424-5p and 
      high mobility group box 3 (HMGB3) was detected by quantitative real-time 
      polymerase chain reaction. Cell viability and cell apoptosis were assessed by 
      cell counting kit-8 (CCK-8) assay and flow cytometry analysis, respectively. 
      Enzyme-linked immunosorbent assay was performed to determine the production of 
      interleukin-1beta (IL-1beta), IL-6, tumor necrosis factor-alpha (TNF-alpha) and monocyte 
      chemotactic protein 1 (MCP-1). Caspase-3 activity was detected by caspase-3 
      activity assay. Protein expression of inducible NOS (iNOS), cyclooxygenase-2 
      (COX2), p-p65 and p65 was analyzed by Western blot. The interactions among 
      circSLCO3A1, miR-424-5p and HMGB3 were identified by dual-luciferase reporter 
      assay, RNA immunoprecipitation assay and RNA pull-down assay. RESULTS: 
      CircSLCO3A1 and HMGB3 expression were significantly increased, while miR-424-5p 
      was decreased in LPS-treated HPAEpiCs and the serum of septic ALI patients in 
      comparison with controls. CircSLCO3A1 knockdown assuaged LPS-induced HPAEpiC 
      inflammation and apoptosis. Besides, circSLCO3A1 targeted miR-424-5p and 
      regulated LPS-triggered HPAEpiC inflammation and apoptosis by binding to 
      miR-424-5p. Under the treatment of LPS, miR-424-5p mediated HPAEpiC disorders by 
      targeting HMGB3. Importantly, circSLCO3A1 modulated HMGB3 production by 
      interacting with miR-424-5p. CONCLUSION: CircSLCO3A1 absence assuaged LPS-induced 
      HPAEpiC inflammation and apoptosis through the miR-424-5p/HMGB3 axis. HIGHLIGHTS: 
      CircSLCO3A1 expression was upregulated in LPS-induced HPAEpiCs and sepsis-induced 
      ALI patients.CircSLCO3A1 depletion protected against LPS-induced HPAEpiC 
      disorders.CircSLCO3A1 bound to miR-424-5p in HPAEpiCs.MiR-424-5p targeted HMGB3 
      in HPAEpiCs.CircSLCO3A1 regulated HMGB3 expression through miR-424-5p. 
      SUPPLEMENTARY INFORMATION: The online version contains supplementary material 
      available at 10.1007/s13273-023-00341-6.
CI  - (c) The Author(s) under exclusive licence to The Korean Society of Toxicogenomics 
      and Toxicoproteomics 2023, Springer Nature or its licensor (e.g. a society or 
      other partner) holds exclusive rights to this article under a publishing 
      agreement with the author(s) or other rightsholder(s); author self-archiving of 
      the accepted manuscript version of this article is solely governed by the terms 
      of such publishing agreement and applicable law.
FAU - Li, Yan
AU  - Li Y
AD  - Department of Emergency Medicine, China-Japan Union Hospital of Jilin University, 
      Changchun, Jilin China. GRID: grid.415954.8. ISNI: 0000 0004 1771 3349
FAU - Zhang, Chunmei
AU  - Zhang C
AD  - Department of Critical Medicine, China-Japan Union Hospital of Jilin University, 
      No. 126, Xiantai Street, Changchun, 130033 Jilin China. GRID: grid.415954.8. 
      ISNI: 0000 0004 1771 3349
FAU - Zhao, Zhongyan
AU  - Zhao Z
AUID- ORCID: 0000-0003-2599-3670
AD  - Department of Critical Medicine, China-Japan Union Hospital of Jilin University, 
      No. 126, Xiantai Street, Changchun, 130033 Jilin China. GRID: grid.415954.8. 
      ISNI: 0000 0004 1771 3349
LA  - eng
PT  - Journal Article
DEP - 20230525
PL  - Korea (South)
TA  - Mol Cell Toxicol
JT  - Molecular & cellular toxicology
JID - 101486570
PMC - PMC10211294
OTO - NOTNLM
OT  - ALI
OT  - CircSLCO3A1
OT  - HMGB3
OT  - miR-424-5p
COIS- Conflict of interestAuthor Yan Li declares that he has no conflict of interest. 
      Author Chunmei Zhang declares that he has no conflict of interest. Author 
      Zhongyan Zhao declares that he has no conflict of interest.
EDAT- 2023/06/26 19:07
MHDA- 2023/06/26 19:07
PMCR- 2023/05/25
CRDT- 2023/06/26 12:21
PHST- 2023/02/16 00:00 [accepted]
PHST- 2023/06/26 19:07 [pubmed]
PHST- 2023/06/26 19:07 [medline]
PHST- 2023/06/26 12:21 [entrez]
PHST- 2023/05/25 00:00 [pmc-release]
AID - 341 [pii]
AID - 10.1007/s13273-023-00341-6 [doi]
PST - aheadofprint
SO  - Mol Cell Toxicol. 2023 May 25:1-12. doi: 10.1007/s13273-023-00341-6.