Protection of Islet Beta Cells from Iron Overload-Induced Injury by Long Non-Coding RNA Maternally Expressed Gene 3

Patients with beta-thalassemia major (β-TM) commonly present with abnormal glucose metabolism, and factors such as iron overload, chronic anaemia, hormonal imbalances, liver dysfunction and inflammation-associated insulin resistance are considered important contributors to pancreatic islet dysfunction. Long non-coding ribonucleic acids (lncRNAs) are increasingly recognised for their regulatory roles in cell apoptosis and glucose homeostasis. This study explores the function of the lncRNA, maternally expressed gene 3 (MEG3), in iron-induced islet β-cell injury. An iron-overload mouse model was induced via intraperitoneal injection of iron dextran. Iron deposition and tissue damage in the pancreas were evaluated using Prussian blue and hematoxylin and eosin staining, and MEG3 expression was quantified via reverse transcription polymerase chain reaction (RT-PCR). In vitro, MIN6 cells were transfected with MEG3 small interfering RNA to examine apoptosis via flow cytometry, and NF-kappa (ĸ)B signaling pathway activity was assessed by Western blotting. Histological staining confirmed significant iron deposition and structural damage in the pancreatic tissue of iron-overloaded mice. The RT-PCR analysis revealed a marked reduction of MEG3 expression in the pancreas (p<0.05). In vitro, MEG3 knockdown significantly increased apoptosis of MIN6 cells compared with controls. Western blot analysis showed an elevated level of NF-ĸB, indicating activation of the NF-ĸB signaling pathway in MEG3-silenced cells. These findings suggest that MEG3 downregulation may enhance islet β-cell apoptosis via NF-ĸB signaling under iron overload conditions. The MEG3 gene may play a protective role against iron-induced islet β-cell apoptosis, potentially involving modulation of the NF-ĸB pathway. This mechanism may contribute to islet dysfunction in patients with β-TM with iron overload.