Published online Jul 15, 2023. doi: 10.4239/wjd.v14.i7.1077
Peer-review started: March 6, 2023
First decision: March 14, 2023
Revised: March 27, 2023
Accepted: April 27, 2023
Article in press: April 27, 2023
Published online: July 15, 2023
Processing time: 129 Days and 0.2 Hours
Cataract remains a prime reason for visual disturbance and blindness all over the world, despite successful surgical replacement with artificial lenses. Diabetic cataract (DC) usually occurs at an earlier age with more rapid progression than age-related cataracts. The polyol pathway, oxidative stress, and nonenzymatic glycation have been shown to be linked to the pathogenesis of DC. But the exact molecular mechanisms underlying DC progression remains largely unknown. As environmental factors play critical roles in the pathogenesis of diabetes mellitus, epigenetic changes may be particularly important.
Despite successful surgical replacement with artificial lenses, cataract remains a prime reason for visual disturbance and blindness globally. It has been recently suggested that N6-methyladenosine (m6A) plays a role in DC progression. However, there exists a lack of understanding regarding RNA m6A modifications and the role of m6A in DC pathogenesis.
To investigate the roles played by altered m6A and differentially expressed mRNAs (DEmRNAs) in DC.
M6A epitranscriptomic microarray was used to investigate altered m6A modifications and determine DEmRNAs. The possible roles played by dysregulated m6A modification was predicted through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Real-time polymerase chain reaction was carried out to identify dysregulated expression patterns of RNA methyltransferases, demethylases, and readers.
Increased m6A abundance levels were found in the total mRNA of DC samples. Bioinformatics analysis predicted that ferroptosis pathways could be associated with m6A-modified mRNAs. The levels of five methylation-related genes-RBM15, WTAP, ALKBH5, FTO, and YTHDF1-were upregulated in DC samples. Upregulation of RBM15 expression was verified in SRA01/04 cells with high-glucose medium and in samples from patients with DC.
M6A abundance level in total mRNA increased in patients with DC. Ferroptosis pathways could be associated with m6A-modified mRNAs.
M6A mRNA modifications may be involved in DC progression via the ferroptosis pathway.