Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Jul 15, 2023; 14(7): 1077-1090
Published online Jul 15, 2023. doi: 10.4239/wjd.v14.i7.1077
Analysis of N6-methyladenosine-modified mRNAs in diabetic cataract
Lei Cai, Xiao-Yan Han, Dan Li, Dong-Mei Ma, Yu-Meng Shi, Yi Lu, Jin Yang
Lei Cai, Xiao-Yan Han, Dan Li, Dong-Mei Ma, Yu-Meng Shi, Yi Lu, Jin Yang, Department of Ophthalmology, Eye, Ear, Nose, and Throat Hospital of Fudan University, Shanghai 200031, China
Lei Cai, Xiao-Yan Han, Dan Li, Dong-Mei Ma, Yu-Meng Shi, Yi Lu, Jin Yang, Key Laboratory of Myopia, Ministry of Health, Shanghai 200031, China
Lei Cai, Xiao-Yan Han, Dan Li, Dong-Mei Ma, Yu-Meng Shi, Yi Lu, Jin Yang, Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai 200031, China
Lei Cai, Xiao-Yan Han, Dan Li, Dong-Mei Ma, Yu-Meng Shi, Yi Lu, Jin Yang, Visual Rehabilitation Professional Committee, Chinese Association of Rehabilitation Medicine, Shanghai 200031, China
Dan Li, State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai 200031, China
Author contributions: Cai L and Han XY contributed equally to this work; Lu Y and Yang J contributed equally to this work; Cai L performed the experiments, analyzed the data, and wrote the original draft; Han XY collected the samples, performed the experiments, and also wrote the original draft; Li D designed the experiments; Ma DM and Shi YM performed the experiments; Lu Y and Yang J designed the experiments and revised the draft; and all authors read and approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 82171039.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of the Eye and ENT Hospital of Fudan University (approval No. 2013021).
Informed consent statement: Written informed consent was obtained from all patients.
Conflict-of-interest statement: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Data sharing statement: The data for this study can be obtained from the corresponding author upon request.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jin Yang, MD, Chief Physician, Department of Ophthalmology, Eye, Ear, Nose, and Throat Hospital of Fudan University, No. 83 Fenyang Road, Shanghai 200031, China. jin_er76@hotmail.com
Received: March 6, 2023
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
Abstract
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.

Keywords: N6-methyladenosine; Diabetic cataract; RNA; Ferroptosis; Epitranscriptomic microarray

Core Tip: Diabetic cataracts (DCs) are associated with elevated blood sugar levels and usually occur at an earlier age with more rapid progression than age-related cataracts. However, the specific molecular mechanisms underlying DC progression remain to be elucidated. As environmental factors are essential in the pathogenesis of diabetes mellitus, epigenetic changes may be particularly important. Recently, N6-methyladenosine (m6A) has been suggested to play a part in DC progression. The present study elucidated the m6A landscape in DC and simultaneously analyzed the methylation and expression of related mRNA. These analyses indicate that m6A mRNA modifications in lens epithelial cells might be involved in DC progression.