LncRNA BRE-AS1 regulates the JAK2/STAT3-mediated inflammatory activation via the miR-30b-5p/SOC3 axis in THP-1 cells.
Humans
STAT3 Transcription Factor
/ metabolism
Janus Kinase 2
/ metabolism
RNA, Long Noncoding
/ genetics
MicroRNAs
/ genetics
THP-1 Cells
Lipopolysaccharides
/ pharmacology
Signal Transduction
Inflammation
/ metabolism
Suppressor of Cytokine Signaling 3 Protein
/ metabolism
Gene Expression Regulation
Macrophages
/ metabolism
Suppressor of Cytokine Signaling Proteins
/ metabolism
JAK2
LncRNA
SOCS3
STAT3
miRNA
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
28 10 2024
28 10 2024
Historique:
received:
06
03
2024
accepted:
21
10
2024
medline:
29
10
2024
pubmed:
29
10
2024
entrez:
29
10
2024
Statut:
epublish
Résumé
Long non-coding RNAs (lncRNAs) have emerged as pivotal regulators in numerous biological processes, including macrophage-mediated inflammatory responses, which play a critical role in the progress of diverse diseases. This study focuses on the regulatory function of lncRNA brain and reproductive organ-expressed protein (BRE) antisense RNA 1 (BRE-AS1) in modulating the inflammatory activation of monocytes/macrophages. Employing the THP-1 cell line as a model, we demonstrate that lipopolysaccharide (LPS) treatment significantly upregulates BRE-AS1 expression. Notably, specific knockdown of BRE-AS1 via siRNA transfection enhances LPS-induced expression of interleukin (IL)-6 and IL-1β, while not affecting tumor necrosis factor (TNF)-α levels. This selective augmentation of pro-inflammatory cytokine production coincides with increased phosphorylation of Janus kinase (JAK)2 and signal transducer and activator of transcription (STAT)3. Furthermore, BRE-AS1 suppression results in the downregulation of suppressor of cytokine signaling (SOCS)3, an established inhibitor of the JAK2/STAT3 pathway. Bioinformatics analysis identified binding sites for miR-30b-5p on both BRE-AS1 and SOCS3 mRNA. Intervention with a miR-30b-5p inhibitor and a synthetic RNA fragment that represents the miR-30b-5p binding site on BRE-AS1 attenuates the pro-inflammatory effects of BRE-AS1 knockdown. Conversely, a miR-30b-5p mimic replicated the BRE-AS1 attenuation outcomes. Our findings elucidate the role of lncRNA BRE-AS1 in modulating inflammatory activation in THP-1 cells via the miR-30b-5p/SOCS3/JAK2/STAT3 signaling pathway, proposing that manipulation of macrophage BRE-AS1 activity may offer a novel therapeutic avenue in diseases characterized by macrophage-driven pathogenesis.
Identifiants
pubmed: 39468152
doi: 10.1038/s41598-024-77265-1
pii: 10.1038/s41598-024-77265-1
doi:
Substances chimiques
STAT3 Transcription Factor
0
Janus Kinase 2
EC 2.7.10.2
RNA, Long Noncoding
0
MicroRNAs
0
JAK2 protein, human
EC 2.7.10.2
STAT3 protein, human
0
Lipopolysaccharides
0
SOCS3 protein, human
0
Suppressor of Cytokine Signaling 3 Protein
0
MIRN30b microRNA, human
0
Suppressor of Cytokine Signaling Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
25726Subventions
Organisme : National Research Foundation of Korea (NRF)
ID : 2022R1A2C1010005
Informations de copyright
© 2024. The Author(s).
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