The circular RNA hsa_circ_0003091 regulates sepsis-induced lung injury by sponging the miR-149/Smad2 axis

Shen, Ming-Yi; Yan, shentao; Zhang, Xiaoyan; Li, Wen; Chen, Xu; Zheng, Xiaoxiao; Zhang, Guoqiang; Sun, Lichao

doi:10.18632/aging.204125

Cited by 8 publications

(6 citation statements)

References 24 publications

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“…These studies provided references for our study, and we constructed sepsis-induced ALI models by treating mice or A549 cells with LPS to explore the functional role of circTDRD9. CircTDRD9 was previously recorded to be upregulated in mice with the tracheal administration of LPS (15). Consistent with the previous data, our study presented that the expression of circTDRD9 was increased in LPS-treated A549 cells.…”

Section: Discussionmentioning

confidence: 99%

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

Zhang,

Dang,

Liu

et al. 2023

Shock

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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.

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Section: Discussionmentioning

confidence: 99%

“…RNA sequencing provided numerous circRNAs that were differently expressed in LPS-induced sepsis in animal models (13,14). Among these circRNAs, we found that circ_0033530 was shown to be significantly upregulated in sepsis patients (15). Circ_0033530 is produced from tudor domain containing 9 (TDRD9), also named circTDRD9 in this study.…”

Section: Introductionmentioning

confidence: 99%

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

Zhang,

Dang,

Liu

et al. 2023

Shock

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“…In addition, circBIRC6 contains miR-145 and miR-34a binding sites to regulate human cell pluripotency ( Yu et al, 2017 ). Some other circRNAs also can sponge microRNAs, despite the majority of them only have a limited amount of microRNA binding sites ( Panda 2018 ; Qiu et al, 2021 ; Shen et al, 2022 ). Further researches are required to identify in what extend circRNAs could sponge microRNAs due to the lower expression of circRNAs.…”

Section: Acting As Microrna Spongesmentioning

confidence: 99%

Functions and clinical significance of circular RNAs in acute myeloid leukemia

et al. 2022

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Circular RNAs (circRNAs) are a class of covalently closed single-stranded RNA molecules. Four types of circRNAs have been reported in animal cells, and they have typical characteristics in their biogenesis, nuclear export and degradation. Advances in our understanding of the molecular functions of circRNAs in sponging microRNAs, modulating transcription, regulating RNA-binding proteins, as well as encoding proteins have been made very recently. Dysregulated circRNAs are associated with human diseases such as acute myeloid leukemia (AML). In this review, we focus on the recently described mechanisms, role and clinical significance of circRNAs in AML. Although great progress of circRNAs in AML has been achieved, substantial efforts are still required to explore whether circRNAs exert their biological function by other mechanisms such as regulation of gene transcription or serving as translation template in AML. It is also urgent that researchers study the machineries regulating circRNAs fate, the downstream effectors of circRNAs modulatory networks, and the clinical application of circRNAs in AML.

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“…For instance, circHIPK3 serves as a sponge for miR-29b to enhance the repair of intestinal epithelial cells in patients with sepsis [16]. Furthermore, circTLK1 promotes inflammation and oxidative stress via the miR-106a-5p/HMGB1 axis in sepsis-associated acute kidney injury, and hsa_circ_0003091 mediates sepsisinduced lung injury by reducing miR-149 [17,18]. Although several studies have revealed that circRNAs are involved in intestinal epithelial injury in sepsis [16,19,20], few studies have investigated the roles of circRNAs in intestinal epithelial apoptosis.…”

Section: Introductionmentioning

confidence: 99%

circFLNA promotes intestinal injury during abdominal sepsis through Fas-mediated apoptosis pathway by sponging miR-766-3p

Shi

Zhang

et al. 2023

Inflamm. Res.

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Background Intra-abdominal infections are the second most common cause of sepsis in the intensive care unit. Intestinal epithelial injury due to abdominal sepsis results in a variety of pathological changes, such as intestinal bacteria and toxins entering the blood, leading to persistent systemic inflammation and multiple organ dysfunction. The increased apoptosis of intestinal epithelial cells induced by sepsis further exacerbates the progression of sepsis. Although several studies have revealed that circRNAs are involved in intestinal epithelial injury in sepsis, few studies have identified the roles of circRNAs in intestinal epithelial apoptosis. Methods We used laser capture microdissection to obtain purified epithelial cells located in intestinal crypts from four patients with abdominal sepsis induced by intestinal perforation and four samples from age and sex-matched non-septic patients. Microarray analysis of circRNAs was conducted to assess differentially expressed circRNAs between patients with and without sepsis. Lastly, in vitro and in vivo assays were performed to study the mechanism of circFLNA in intestinal epithelial apoptosis during sepsis. Results circFLNA was upregulated in the intestinal epithelium after abdominal sepsis induced by intestinal perforation. Inhibition of miR-766-3p impaired si-circFLNA-mediated inhibition of apoptosis and inflammation factor levels in lipopolysaccharide (LPS)-treated HIEC-6 cells. circFLNA aggravated apoptosis and inflammation through the Fas-mediated apoptosis pathway in both LPS-treated HIEC-6 cells and a mouse cecal ligation and puncture model. Conclusion Our findings showed that circFLNA promotes intestinal injury in abdominal sepsis through the Fas-mediated apoptosis pathway by sponging miR-766-3p. The circFLNA/miR-766-3p/Fas axis has potential as a novel therapeutic target for treating intestinal injury in sepsis.

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The circular RNA hsa_circ_0003091 regulates sepsis-induced lung injury by sponging the miR-149/Smad2 axis

Cited by 8 publications

References 24 publications

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

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

Functions and clinical significance of circular RNAs in acute myeloid leukemia

circFLNA promotes intestinal injury during abdominal sepsis through Fas-mediated apoptosis pathway by sponging miR-766-3p

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