CIRCTDRD9 CONTRIBUTES TO SEPSIS-INDUCED ACUTE LUNG INJURY BY ENHANCING THE EXPRESSION OF RAB10 VIA DIRECTLY BINDING TO MIR-223-3P.
Shock
; 60(2): 206-213, 2023 08 01.
Article
em En
| MEDLINE
| ID: mdl-37548713
ABSTRACT
ABSTRACT Background:
The dysregulation of circular RNAs (circRNAs) is involved in various human diseases, including sepsis-induced acute lung injury (ALI). We aimed to investigate the role of circTDRD9 in the development of sepsis-induced ALI.Methods:
Cell models of sepsis-induced ALI were established by treating A549 cells with LPS. The expression of circTDRD9, miR-223-3p, and RAB10 mRNA was measured by quantitative real-time PCR (qPCR). The levels of inflammatory factors were measured by ELISA. Oxidative stress-related indicators were monitored by using commercial detection kits. The expression of fibrosis-related proteins was detected by Western blot assay. Cell proliferation was assessed by EdU assay. The predicted binding relationship between miR-223-3p and circTDRD9 or RAB10 was verified by dual-luciferase reporter assay, RIP assay or pull-down assay.Results:
CircTDRD9 was highly expressed in LPS-treated A549 cells. CircTDRD9 downregulation prevented LPS-induced inflammation, oxidative stress, cell proliferation inhibition, and cell fibrosis in A549 cells, whereas these effects were reversed by the inhibition of miR-223-3p, a target of circTDRD9. In addition, RAB10 was verified as a target of miR-223-3p, and RAB10 overexpression recovered LPS-induced inflammation, oxidative stress, cell proliferation inhibition, and cell fibrosis in A549 cells that were ameliorated by miR-223-3p restoration. Importantly, circTDRD9 positively regulated RAB10 expression by binding to miR-223-3p.Conclusion:
CircTDRD9 overexpression was closely associated with LPS-induced ALI. CircTDRD9 contributed to LPS-induced ALI partly by upregulating RAB10 via binding to miR-223-3p.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Sepse
/
MicroRNAs
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Lesão Pulmonar Aguda
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article