CircTDRD9 contributes to sepsis-induced acute lung injury by enhancing the expression of RAB10 via directly binding to miR-223-3p

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 .

文章引用产品列表