Circular RNA HIPK3 aggravates sepsis-induced acute kidney injury via modulating the microRNA-338/forkhead box A1 axis.

Abstract

Circular RNAs (circRNAs) have been extensively studied in various diseases, including sepsis-induced acute kidney injury (AKI). This research intended to elucidate the mechanism of circular RNA HIPK3 (circHIPK3) in sepsis-engendered AKI. Human tubule epithelial cells (HK2) were stimulated with lipopolysaccharide (LPS) to establish a septic AKI cell model. The gene expression levels were evaluated by RT-qPCR. Cell viability, apoptosis, and cell cycle distribution were assessed through CCK-8 and flow cytometry assays. The potential interactions between genes were verified by luciferase reporter and RIP assays. The results displayed that circHIPK3 expression was enhanced in septic AKI patients and LPS-triggered HK2 cells. Moreover, circHIPK3 interference expedited HK2 cell viability and attenuated apoptosis, inflammatory and oxidative damages following LPS stimulation. Furthermore, circHIPK3 functioned as a molecular sponge for miR-338, and forkhead box A1 (FOXA1) was negatively regulated by miR-338. CircHIPK3 aggravated cell injury in LPS-treated HK2 via targeting miR-338, and FOXA1 addition overturned the suppressing impacts of miR-338-3p augmentation on LPS-activated HK2 cell damage. Finally, we demonstrated that circHIPK3 modulated LPS-induced cell damage via the miR-338/FOXA1 axis. In sum, our results elaborated that circHIPK3 knockdown attenuated LPS-triggered HK2 cell injury by regulating FOXA1 expression via interacting with miR-338, suggesting that circHIPK3 might be a potential biomarker and therapeutic target for sepsis-induced AKI patients.

• Authors: Hulin Lu, Yan Chen, Xiaoyi Wang, Yong Yang, Min Ding, Fengping Qiu
• Journal: Bioengineered (Bioengineered) Vol. 13 Issue 3 Pg. 4798-4809 (03 2022) ISSN: 2165-5987 [Electronic] United States
• PMID: 35148669 (Publication Type: Journal Article)

Chemical References

• FOXA1 protein, human
• Hepatocyte Nuclear Factor 3-alpha
• Intracellular Signaling Peptides and Proteins
• Lipopolysaccharides
• MIRN338 microRNA, human
• MicroRNAs
• RNA, Circular
• HIPK3 protein, human
• Protein Serine-Threonine Kinases

Topics

• Acute Kidney Injury (genetics)
• Apoptosis (genetics)
• Hepatocyte Nuclear Factor 3-alpha (metabolism)
• Humans
• Intracellular Signaling Peptides and Proteins
• Lipopolysaccharides (pharmacology)
• MicroRNAs (genetics, metabolism)
• Protein Serine-Threonine Kinases (genetics)
• RNA, Circular (genetics)
• Sepsis (complications, genetics, metabolism)