Circtdrd9 Contributes to Sepsis-Induced Acute Lung Injury by Enhancing the Expression of Rab10 via Directly Binding to Mir-223-3p

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.

Analysis and Identification of Ferroptosis-Related Gene Signature for Acute Lung Injury

“…The role of these proteins in ferroptosis-induced ALI should be confirmed in the future. In addition, although we analyzed miRNAs targeting key genes, miRNAs also involved in the occurrence of ALI (48), we did not predict the lncRNAs related to the upstream regulation of miRNAs. miRNA expression is influenced by upstream molecules such as lncRNAs, which can also serve as targets for disease treatment and diagnosis.…”

Functional roles of circular RNAs in lung injury

“…The increased HECTD1 protein expression is associated with macrophage activation and contributing to the progression of silicosis ( Fang et al, 2018 ; Zhou et al, 2018 ). It is found that circRNA11:120406118|12040782 was increased in the peripheral serum of silicosis patients, which facilitated the progress of silicosis by aggravating NLRP3-mediated macrophages pyroptosis through sponging miR-30b-5p ( Zhang et al, 2023 ).…”