Has_circRNA_0122683 (circ-PRKCI) relieves ferroptosis of HPAEpiCs in sepsis-induced acute lung injury by sponging miR-382-5p
Circular ribonucleic acid (RNA) protein kinase C iota (circ-PRKCI, hsa_circRNA_0122683) has been previously reported to be involved in the development of sepsis. However, the knowledge regarding the potential role and mechanism of circ-PRKCI in sepsis-induced acute lung injury (ALI) is unclear. An i...
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PeerJ Inc.
2025-05-01
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| author | Limei Yan Xiajun Lu Ning Wang Peng Jia |
| author_facet | Limei Yan Xiajun Lu Ning Wang Peng Jia |
| author_sort | Limei Yan |
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| description | Circular ribonucleic acid (RNA) protein kinase C iota (circ-PRKCI, hsa_circRNA_0122683) has been previously reported to be involved in the development of sepsis. However, the knowledge regarding the potential role and mechanism of circ-PRKCI in sepsis-induced acute lung injury (ALI) is unclear. An in vitro cellular model of sepsis-ALI was simulated by the treatment of lipopolysaccharide (LPS) in human pulmonary alveolar epithelial cells (HPAEpiCs). The expression of circ-PRKCI in plasma samples from sepsis patients with or without ALI as well as sepsis-ALI cell model was determined by quantitative real-time PCR (qRT-PCR). The diagnostic utility of circ-PRKCI was analyzed using receiver operating characteristic (ROC) curves. The levels of iron content (Fe2+), glutathione (GSH), malondialdehyde (MDA), and reactive oxygen species (ROS) were detected using corresponding commercial kits. The assessment of cell viability and production of pro-infammatory cytokines (IL-6, IL-1β and TNF-α) was measured using Cell Counting Kit-8 (CCK-8) and enzyme-linked immunosorbent assay (ELISA). The targeting relationship between circ-PRKCI and miR-382-5p was predicted by bioinformatics analysis, and subsequently confirmed by luciferase reporter and RNA immunoprecipitation (RIP) assays. Results shows that decreased circ-PRKCI expression but increased miR-382-5p expression was observed in sepsis patients with ALI and sepsis-induced ALI cell model. The area under the curve values of ROC curves for circ-PRKCI in differentiating septic ALI patients from healthy individuals and septic non-ALI patients were 0.996 and 0.999, respectively. Functional in vitro assays revealed that enforced expression of circ-PRKCI alleviated LPS-induced ferroptosis and inflammatory response of HPAEpiCs, which were reversed by Erastin or FIN56 administration. Mechanistically, circ-PRKCI was identified as a sponge of miR-382-5p and negatively regulated miR-382-5p expression. Further rescue experiments showed that miR-382-5p overexpression could compromise the anti-ferroptosis and anti-inflammatory response effects of circ-PRKCI on LPS-induced injury of HPAEpiCs. Our study demonstrated that circ-PRKCI may be a promising biomarker for septic ALI diagnosis. circ-PRKCI inhibits ferroptosis and inflammatory response in sepsis-induced ALI by sponging miR-382-5p, indicating that the circ-PRKCI/miR-382-5p axis might be a novel therapeutic target for the treatment of sepsis-induced ALI. |
| format | Article |
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| spelling | doaj-art-2cc2e940974a4d78917aae73afeb26502025-08-20T01:50:59ZengPeerJ Inc.PeerJ2167-83592025-05-0113e1940410.7717/peerj.19404Has_circRNA_0122683 (circ-PRKCI) relieves ferroptosis of HPAEpiCs in sepsis-induced acute lung injury by sponging miR-382-5pLimei Yan0Xiajun Lu1Ning Wang2Peng Jia3Intensive Care Medicine Department, The People’s Hospital of Suzhou New District, Suzhou, ChinaIntensive Care Medicine Department, The People’s Hospital of Suzhou New District, Suzhou, ChinaIntensive Care Medicine Department, The People’s Hospital of Suzhou New District, Suzhou, ChinaTrauma Orthopedics, The People’s Hospital of Suzhou New District, Suzhou, ChinaCircular ribonucleic acid (RNA) protein kinase C iota (circ-PRKCI, hsa_circRNA_0122683) has been previously reported to be involved in the development of sepsis. However, the knowledge regarding the potential role and mechanism of circ-PRKCI in sepsis-induced acute lung injury (ALI) is unclear. An in vitro cellular model of sepsis-ALI was simulated by the treatment of lipopolysaccharide (LPS) in human pulmonary alveolar epithelial cells (HPAEpiCs). The expression of circ-PRKCI in plasma samples from sepsis patients with or without ALI as well as sepsis-ALI cell model was determined by quantitative real-time PCR (qRT-PCR). The diagnostic utility of circ-PRKCI was analyzed using receiver operating characteristic (ROC) curves. The levels of iron content (Fe2+), glutathione (GSH), malondialdehyde (MDA), and reactive oxygen species (ROS) were detected using corresponding commercial kits. The assessment of cell viability and production of pro-infammatory cytokines (IL-6, IL-1β and TNF-α) was measured using Cell Counting Kit-8 (CCK-8) and enzyme-linked immunosorbent assay (ELISA). The targeting relationship between circ-PRKCI and miR-382-5p was predicted by bioinformatics analysis, and subsequently confirmed by luciferase reporter and RNA immunoprecipitation (RIP) assays. Results shows that decreased circ-PRKCI expression but increased miR-382-5p expression was observed in sepsis patients with ALI and sepsis-induced ALI cell model. The area under the curve values of ROC curves for circ-PRKCI in differentiating septic ALI patients from healthy individuals and septic non-ALI patients were 0.996 and 0.999, respectively. Functional in vitro assays revealed that enforced expression of circ-PRKCI alleviated LPS-induced ferroptosis and inflammatory response of HPAEpiCs, which were reversed by Erastin or FIN56 administration. Mechanistically, circ-PRKCI was identified as a sponge of miR-382-5p and negatively regulated miR-382-5p expression. Further rescue experiments showed that miR-382-5p overexpression could compromise the anti-ferroptosis and anti-inflammatory response effects of circ-PRKCI on LPS-induced injury of HPAEpiCs. Our study demonstrated that circ-PRKCI may be a promising biomarker for septic ALI diagnosis. circ-PRKCI inhibits ferroptosis and inflammatory response in sepsis-induced ALI by sponging miR-382-5p, indicating that the circ-PRKCI/miR-382-5p axis might be a novel therapeutic target for the treatment of sepsis-induced ALI.https://peerj.com/articles/19404.pdfcirc-PRKCISepsis-induced ALIHPAEpiCsFerroptosismiR-382-5p |
| spellingShingle | Limei Yan Xiajun Lu Ning Wang Peng Jia Has_circRNA_0122683 (circ-PRKCI) relieves ferroptosis of HPAEpiCs in sepsis-induced acute lung injury by sponging miR-382-5p PeerJ circ-PRKCI Sepsis-induced ALI HPAEpiCs Ferroptosis miR-382-5p |
| title | Has_circRNA_0122683 (circ-PRKCI) relieves ferroptosis of HPAEpiCs in sepsis-induced acute lung injury by sponging miR-382-5p |
| title_full | Has_circRNA_0122683 (circ-PRKCI) relieves ferroptosis of HPAEpiCs in sepsis-induced acute lung injury by sponging miR-382-5p |
| title_fullStr | Has_circRNA_0122683 (circ-PRKCI) relieves ferroptosis of HPAEpiCs in sepsis-induced acute lung injury by sponging miR-382-5p |
| title_full_unstemmed | Has_circRNA_0122683 (circ-PRKCI) relieves ferroptosis of HPAEpiCs in sepsis-induced acute lung injury by sponging miR-382-5p |
| title_short | Has_circRNA_0122683 (circ-PRKCI) relieves ferroptosis of HPAEpiCs in sepsis-induced acute lung injury by sponging miR-382-5p |
| title_sort | has circrna 0122683 circ prkci relieves ferroptosis of hpaepics in sepsis induced acute lung injury by sponging mir 382 5p |
| topic | circ-PRKCI Sepsis-induced ALI HPAEpiCs Ferroptosis miR-382-5p |
| url | https://peerj.com/articles/19404.pdf |
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