Analysis of N6-methyladenosine-modified mRNAs in diabetic cataract  

作　　者：Lei Cai Xiao-Yan Han Dan Li Dong-Mei Ma Yu-Meng Shi Yi Lu Jin Yang 

机构地区：[1]Department of Ophthalmology,Eye,Ear,Nose,and Throat Hospital of Fudan University,Shanghai 200031,China [2]Key Laboratory of Myopia,Ministry of Health,Shanghai 200031,China [3]Shanghai Key Laboratory of Visual Impairment and Restoration,Shanghai Key Laboratory of Visual Impairment and Restoration,Shanghai 200031,China [4]Visual Rehabilitation Professional Committee,Chinese Association of Rehabilitation Medicine,Shanghai 200031,China [5]State Key Laboratory of Molecular Engineering of Polymers,Fudan University,Shanghai 200031,China

出　　处：《World Journal of Diabetes》2023年第7期1077-1090,共14页世界糖尿病杂志（英文版）（电子版）

基　　金：Supported by the National Natural Science Foundation of China,No.82171039.

摘　　要：BACKGROUND Cataracts remain a prime reason for visual disturbance and blindness all over the world,despite the capacity for successful surgical replacement with artificial lenses.Diabetic cataract(DC),a metabolic complication,usually occurs at an earlier age and progresses faster than age-related cataracts.Evidence has linked N6-methyladenosine(m6A)to DC progression.However,there exists a lack of understanding regarding RNA m6A modifications and the role of m6A in DC pathogenesis.AIM To elucidate the role played by altered m6A and differentially expressed mRNAs(DEmRNAs)in DC.METHODS Anterior lens capsules were collected from the control subjects and patients with DC.M6A epitranscriptomic microarray was performed to investigate the altered m6A modifications and determine the DEmRNAs.Through Gene Ontology and pathway enrichment(Kyoto Encyclopedia of Genes and Genomes)analyses,the potential role played by dysregulated m6A modification was predicted.Real-time polymerase chain reaction was further carried out to identify the dysregulated expression of RNA methyltransferases,demethylases,and readers.RESULTS 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 DC patients.CONCLUSION M6a mRNA modifications may be involved in DC progression via the ferroptosis pathway,rendering novel insights into therapeutic strategies for DC.

关 键 词：N6-methyladenosine Diabetic cataract RNA Ferroptosis Epitranscriptomic microarray 

分 类 号：R587.2[医药卫生—内分泌] R776.1[医药卫生—内科学]