Identification and Verification of Ferroptosis-Related Mirna Regulatory Networks in Patients with Acute Kidney Injury

Abstract

Background: Acute kidney injury (AKI) is a major public health concern, leading to high morbidity and mortality. Despite decades of research, the pathogenesis of AKI remains incompletely clear, and effective therapies and predictive biomarkers are lacking. Ferroptosis is a novel regulated cell death associated with many diseases. This study aims to identify ferroptosis-related microRNA (miRNA) regulatory networks in AKI patients. Method: Single-cell RNA (scRNA)-sequencing data obtained from the kidney and urine of AKI patients underwent bioinformatics analysis to determine the ferroptosis-related miRNA regulatory networks in patients with AKI. Pseudotime trajectory analysis was performed to assess the relationship between the developmental trajectory of the proximal tubule (PT) cells and AKI cells. The competing endogenous RNA (ceRNA) network was constructed using the ferroptosis-associated messenger RNA (mRNA), microRNA (miRNA), and long non-coding RNA (lncRNA). Results: The pseudotime trajectory analysis showed that the developmental trajectory of PT cells exhibited the potential for AKI cell transformation. Ferroptosis pathway enrichment was co-expressed with the developmental trajectory of PT cells. Finally, the identified candidate miRNA screened from three different models (has-miR-3144-3p) was associated with the ferroptosis related ceRNA network with related mRNAs and lncRNAs. Conclusions: In this study, the single-cell data of PT cells derived from urine in AKI patients effectively simulates the developmental trajectory of AKI. Meanwhile, the pseudotime trajectory analysis demonstrated ferroptosis pathway enrichment is co-expressed with the pseudotime trajectory analysis. Therefore, the ferroptosis-associated ceRNA network constructed is helpful for further research.