Alteration of N6-Methyladenosine RNA Profiles in Cisplatin-Induced Acute Kidney Injury in Mice

Area of Science:

• Biochemistry
• Molecular Biology
• Genomics

Background:

• Acute kidney injury (AKI) is a critical clinical condition.
• Cisplatin is a widely used chemotherapeutic agent with known nephrotoxicity.
• N6-methyladenosine (m⁶A) is the most prevalent RNA modification, regulating gene expression.

Purpose of the Study:

• To investigate the dynamic changes in the m⁶A RNA epitranscriptome during cisplatin-induced acute kidney injury (Cis-AKI) in a mouse model.
• To identify specific m⁶A-modified mRNAs and lncRNAs involved in the pathogenesis of Cis-AKI.

Main Methods:

• Measurement of global m⁶A levels and expression of key m⁶A regulators (methyltransferases and demethylases) in kidney tissues.
• Global profiling of m⁶A-methylated RNAs using microarray analysis.
• Bioinformatics analysis to predict the functional implications of differentially methylated RNAs.

Main Results:

• Cisplatin treatment led to increased global m⁶A levels in the kidneys.
• Expression levels of m⁶A regulators, including Mettl3, Mettl14, Wtap, Fto, and Alkbh5, were altered.
• Significant differential methylation was observed in 618 mRNAs and 98 lncRNAs.
• Bioinformatics analysis suggested that methylated mRNAs are primarily involved in metabolic processes.

Conclusions:

• The m⁶A epitranscriptome undergoes significant alterations in Cis-AKI.
• These m⁶A RNA profile changes are potentially implicated in the development of cisplatin-induced nephrotoxicity.
• Targeting m⁶A modification pathways could offer novel therapeutic strategies for Cis-AKI.