Transcriptome sequencing of circular RNA reveals a novel circular RNA-has_circ_0114427 in the regulation of inflammation in acute kidney injury

Abstract

Acute kidney injury (AKI) is a common serious syndrome characterized by rapid decrease of glomerular filtration rate and the progressive increase of serum creatinine. Circular RNAs (circRNAs) are regulatory RNAs that recently became popular among various diseases. However, the expression profile and function of circRNAs in AKI remain largely unknown. The main function of circRNAs is acting as competing endogenous RNAs (ceRNAs) by binding with microRNAs (miRNAs), as indicated by recent research. In the present study, we established cisplatin-induced AKI model in mice and isolated renal tubular tissues to extract circRNAs for next-generation sequencing (NGS) and bioinformatics analysis. We analyzed the composition, distribution and Gene Ontology terms of circRNAs in cisplatin-induced AKI and revealed differentially expressed circRNAs related to AKI. By finding homologous genes between mouse and human, we identified circRNA- circ-0114427 in humans. We further investigated its function in AKI cell model. Circ-0114427 expression was significantly up-regulated in different AKI cell models. Knockdown of circ-0114427 indicated that circ-0114427 bound to miR-494 as a miRNA sponge to regulate ATF3 expression and further affected the expression of downstream cytokine IL-6. Circ-0114427 regulates inflammatory progression in AKI's early stage via circ-0114427/miR-494/ATF3 pathway. Our findings reveal the expression profile of circRNAs in cisplatin-induced AKI and provide a novel insight into the regulatory mechanism of circRNAs, which may become a new molecular target resource for early diagnosis and treatment strategies.