Abstract: SA-PO148
MicroRNA-mRNA Interactions in Cisplatin-Induced AKI to CKD
Session Information
- AKI: Metabolism and Cell Death
October 26, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Sone, Hisakatsu, Augusta University Medical College of Georgia, Augusta, Georgia, United States
- Lee, Tae Jin, Augusta University Medical College of Georgia, Augusta, Georgia, United States
- Lee, Byung Rho, Augusta University Medical College of Georgia, Augusta, Georgia, United States
- Heo, Dan, Augusta University Medical College of Georgia, Augusta, Georgia, United States
- Kwon, Sang-Ho, Augusta University Medical College of Georgia, Augusta, Georgia, United States
Background
Chemotherapy with cisplatin can lead to chronic kidney disease, complicating cancer prognosis. Understanding the interactions between microRNAs (miRNAs) and their target messenger RNAs (mRNAs) can shed light on the biological processes involved in cisplatin-induced kidney injury.
Methods
We used small and total RNA sequencing, and chimeric-eCLIP sequencing to identify pairs of miRNAs and their target mRNAs in the kidneys of cisplatin-injured male mice. These interactions were confirmed using various methods, including database searches, RNAscope, RT-qPCR, immunofluorescence, and immunoblotting.
Results
We identified 55,794 direct miRNA-mRNA interactions in the kidneys. Among the interactions, a group of cisplatin-induced miRNAs enriched with select mRNAs affects mitochondrial metabolic pathways. Specifically, the cisplatin-induced miRNAs, miR-429-3p and miR-21a-5p, suppress the pathway that breaks down branched-chain amino acids (BCAAs) in the proximal tubule, leading to ferroptotic cell death. In contrast, stimulating BCAA catabolism in the injured kidneys reduced ferroptosis and inflammation.
Conclusion
In vivo renal miRNA-mRNA interaction mapping identifies the role of branched-chain amino acid catabolism in ferroptotic proximal tubular cell death. Our findings suggest potential therapeutic benefits in modulating the branched-chain amino acid pathway to alleviate nephrotoxicity.
Funding
- NIDDK Support