CIRCTDRD9 CONTRIBUTES TO SEPSIS-INDUCED ACUTE LUNG INJURY BY ENHANCING THE EXPRESSION OF RAB10 VIA DIRECTLY BINDING TO MIR-223-3P

• Published in: Shock (Augusta, Ga.) Vol. 60; no. 2; pp. 206 - 213
• Main Authors: Zhang, Rui, Dang, Xiaoyan, Liu, Jie, Feng, Hui, Sun, Jiangli, Peng, Zhuo
• Format: Journal Article
• Language: English
• Published: United States 01-08-2023
• Subjects: Acute Lung Injury; Apoptosis; Humans; Inflammation; Lipopolysaccharides - toxicity; MicroRNAs - genetics; Sepsis - complications; Sepsis - genetics
• ISSN: 1073-2322; 1540-0514
• DOI: 10.1097/SHK.0000000000002169

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.