Work

DLX6-AS1 aggravates high glucose-induced retinal pigment epithelial cell dysfunction via the miR-654-3p/HMGB1 pathway in diabetic retinopathy

Year: 2026

Type: article

Abstract: This study explores the association between serum DLX6-AS1 and the presence of diabetic retinopathy (DR), and preliminarily clarifies its regulatory mechanism in high glucose-induced retinal pigment epithelial (RPE) cell injury. Serum levels of DLX6-AS1 were measured via RT-qPCR in type 2 diabetes mellitus (T2DM) patients with and without DR. Association between serum DLX6-AS1 and prevalent DR was analyzed using receiver operating characteristic (ROC) curve and binary logistic regression. In vitro, a high-glucose injury model was established in ARPE-19 cells. Dual luciferase reporter assay and RNA immunoprecipitation were performed to confirm the targeted regulatory interaction within the DLX6-AS1/miR-654-3p/high mobility group box 1 (HMGB1) axis. Changes in apoptosis, oxidative stress, and inflammatory responses after pathway intervention were subsequently evaluated. Apoptosis rate was detected by flow cytometry and caspase activity assay. Oxidative stress status was evaluated by measuring reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD). Inflammatory factors were quantified via RT-qPCR and enzyme-linked immunosorbent assay (ELISA). Serum DLX6-AS1 level was significantly higher in DR patients than in non-DR patients and was significantly associated with the presence of DR. In high-glucose-cultured ARPE-19 cells, DLX6-AS1 interference markedly reduced apoptosis and alleviated oxidative stress and inflammatory responses. This protective effect was partially reversed by miR-654-3p silencing. Mechanistically, DLX6-AS1 upregulated HMGB1 expression via sponging miR-654-3p, and HMGB1 overexpression further significantly attenuated the cytoprotective effect of miR-654-3p. Aberrant serum DLX6-AS1 expression is closely associated with DR status in T2DM patients. The DLX6-AS1/miR-654-3p/HMGB1 axis mediates RPE cell injury under high-glucose conditions in vitro.

Source: European journal of medical research

DOI: 10.1186/s40001-026-05388-4

Authors: Xiao Liu, Yan Zhao, Fang Li, Guowei Huang, Xiaomei Shao

Institutions: Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine of Hebei Province, People's Hospital of Kaizhou District

Language: English

Topic: Retinal Diseases and Treatments

Subfield: Ophthalmology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,190