{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T05:02:19Z","timestamp":1781586139741,"version":"3.54.5"},"reference-count":45,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,2,26]],"date-time":"2024-02-26T00:00:00Z","timestamp":1708905600000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>N6\u2010methyladenosine (m<jats:sup>6<\/jats:sup>A) modification has been reported to have roles in modulating the development of diabetic cataract (DC). Methyltransferase\u2010like 3 (METTL3) is a critical m<jats:sup>6<\/jats:sup>A methyltransferase involving in m<jats:sup>6<\/jats:sup>A modification activation. Here, we aimed to explore the action and mechanism of METTL3\u2010mediated maturation of miR\u20104654 in DC progression. Human lens epithelial cells (HLECs) were exposed to high glucose (HG) to imitate DC condition in\u00a0vitro. Levels of genes and proteins were tested via qRT\u2010PCR and western blotting assays. The proliferation and apoptosis of HLECs were evaluated by cell counting kit\u20108, 5\u2010ethynyl\u20102\u2032\u2010deoxyuridine (EdU), and flow cytometry assays, respectively. Oxidative stress was analyzed by detecting the contents of reactive oxygen species (ROS), superoxide dismutase (SOD) and malondialdehyde (MDA). The binding of miR\u20104654 and SOD2 was confirmed by dual\u2010luciferase reporter assay. The m<jats:sup>6<\/jats:sup>A\u2010RNA immunoprecipitation (MeRIP) assay detected the m<jats:sup>6<\/jats:sup>A modification profile. Thereafter, we found that miR\u20104654 expression was elevated in DC samples and HG\u2010induced HLECs. MiR\u20104654 knockdown reversed HG\u2010mediated apoptosis and oxidative stress in HLECs. Mechanistically, miR\u20104654 directly targeted SOD2, silencing of SOD2 abolished the protective effects of miR\u20104654 knockdown on HLECs under HG condition. In addition, METTL3 induced miR\u20104654 maturation through promoting pri\u2010miR\u20104654 m<jats:sup>6<\/jats:sup>A modification, thereby increasing miR\u20104654 content in HLECs. METTL3 was highly expressed in DC samples and HG\u2010induced HLECs, METTL3 deficiency protected HLECs against HG\u2010mediated apoptotic and oxidative injury via down\u2010regulating miR\u20104654. In all, METTL3 induced miR\u20104654 maturation in a m<jats:sup>6<\/jats:sup>A\u2010dependent manner, which was then reduced SOD2 expression, thus promoting apoptosis and oxidative stress in HLECs, suggesting a novel path for DC therapy.<\/jats:p>","DOI":"10.1111\/cbdd.14491","type":"journal-article","created":{"date-parts":[[2024,2,26]],"date-time":"2024-02-26T08:28:50Z","timestamp":1708936130000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Methyltransferase METTL3\u2010mediated maturation of miR\u20104654 facilitates high glucose\u2010induced apoptosis and oxidative stress in lens epithelial cells via decreasing SOD2"],"prefix":"10.1111","volume":"103","author":[{"given":"Ming","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Jingzhou Hospital Yangtze University, (Jingzhou Central Hospital)  Jingzhou Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanfan","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Jingzhou Hospital Yangtze University, (Jingzhou Central Hospital)  Jingzhou Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Jingzhou Hospital Yangtze University, (Jingzhou Central Hospital)  Jingzhou Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6958-4089","authenticated-orcid":false,"given":"Bo","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine Yangtze University  Jingzhou Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,2,26]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/wrna.1337"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14281"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27030811"},{"issue":"1","key":"e_1_2_9_5_1","first-page":"4","article-title":"General approaches to the stem cell therapy in diabetes mellitus as innovative researches","volume":"1","author":"Alp E. 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