Expression and mechanistic roles of long non-coding RNAs in diabetic cataract: a systematic review and meta-analysis

Diabetic cataract (DC) is a lens-opacity complication of diabetes driven by hyperglycemia-related oxidative, apoptotic, metabolic, and epithelial-mesenchymal transition (EMT) pathways. This review evaluated the expression and mechanistic roles of long non-coding RNAs (lncRNAs) and lncRNA-related epitranscriptomic regulators in DC.

PubMed, Embase, Cochrane Library, Scopus, Web of Science, and Google Scholar were searched to 1 June 2026 without language restriction. Ex vivo, in vitro, transcriptomic, epitranscriptomic, and mechanistic studies were included. Two reviewers screened records, extracted data, and assessed bias using the JBI checklist. Random-effects meta-analysis pooled Fisher-z-transformed correlations; bias and certainty were assessed using funnel plot, exploratory Egger's test, and GRADE-adapted criteria.

Thirteen studies were included. Eight expression datasets showed a significant association between DC and lncRNA or lncRNA-linked epitranscriptomic dysregulation (pooled r = 0.445, 95% CI 0.338-0.541; p = 0.001), with low heterogeneity (I² = 1.2%; Q = 7.088; df = 7; p = 0.42; τ² = 0.00037; τ = 0.019; prediction interval 0.308-0.563). LINC01508, MAFA-AS1, MIAT, GAS5, XIST, MALAT1, KCNQ1OT1, and METTL16 were upregulated, whereas NEAT1 was downregulated. MALAT1, GAS5, XIST, PVT1, KCNQ1OT1, FOXD3-AS1, NEAT1, RMRP, METTL3, METTL16, FTO, METTL14, WTAP, ALKBH5, and YTHDF-family regulators converged on ceRNA signaling, apoptosis, oxidative stress, EMT, proliferation, mitochondrial dysfunction, ICAM-1 stabilization, and m⁶A-linked DKK1/Wnt/β-catenin regulation. Leave-one-out estimates ranged from r = 0.422 to 0.502; year-based meta-regression did not materially change the result.

DC is associated with coordinated lncRNA and epitranscriptomic dysregulation across oxidative, apoptotic, EMT, mitochondrial, proliferative, and m⁶A-regulated pathways.

Not applicable.