The lncRNA CASC9 alleviates lipopolysaccharide-induced acute kidney injury by regulating the miR-424-5p/TXNIP pathway

Abstract

Objective This study aimed to clarify the mechanism by which the long non-coding RNA cancer susceptibility candidate 9 (CASC9) alleviates sepsis-related acute kidney injury (S-AKI). Methods A lipopolysaccharide (LPS)-induced AKI model was established to simulate S-AKI. HK-2 human renal tubular epithelial cells were treated with LPS to establish an in vitro model, and mice were intraperitoneally injected with LPS to generate an in vivo model. Subsequently, the mRNA expression of inflammatory and antioxidant factors was validated by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Reactive oxygen species (ROS) production was assessed using an assay kit. Apoptosis was detected by western blotting and fluorescence-activated cell sorting. Results CASC9 was significantly downregulated in the LPS-induced AKI model. CASC9 attenuated cell inflammation and apoptosis and enhanced the antioxidant capacity of cells. Regarding the mechanism, miR-424-5p was identified as the downstream target of CASC9, and the interaction between CASC9 and miR-424-5p promoted thioredoxin-interacting protein (TXNIP) expression. Conclusions CASC9 alleviates LPS-induced AKI in vivo and in vitro, and CASC9 directly targets miR-424-5p and further promotes the expression of TXNIP. We have provided a possible reference strategy for the treatment of S-AKI.

MiR-424/TGIF2-Mediated Pro-Fibrogenic Responses in Oral Submucous Fibrosis

“…In an effort to evaluate the role of miR-424 in oxidative stress accumulation, an miR-424 inhibitor was applied, and we showed that ROS generation was suppressed. Our findings were consistent with another study showing that miR-424 conferred to the LPS-induced ROS production in lipopolysaccharide (LPS)-treated pulmonary alveolar epithelial cells [ 29 ] or LPS-stimulated proximal tubule epithelial cells [ 30 ]. However, miR-424 was revealed to abrogate oxidative stress-associated injury by increasing antioxidant enzymes and reducing oxidative stress indicators in C57/BL6 mice with transient cerebral ischemia [ 18 ].…”

The Intersection of Acute Kidney Injury and Non-Coding RNAs: Inflammation

“…Wang et al found that XIST acts as a ceRNA for miRNA-155-5p to suppress inflammation and apoptosis, thereby attenuating sepsis-induced AKI( Wang and Cao, 2022 ). Furthermore, Fan et al found that the CASC9 could attenuate LPS-induced acute renal inflammatory injury via the miRNA-424-5p/TXNIP axis ( Fan et al, 2021 ). The latest research showed that NORAD knockdown alleviated kidney injury in mice and decreased the inflammatory response and apoptosis of LPS-stimulated HK-2 cells via the miRNA-577/GOLPH3 axis ( Xie et al, 2022 ).…”