miR-103a regulates DNA repair capacity in human astrocytes under oxidative stress through direct OGG1 targeting.

backgroundDeficient DNA repair capacity contributes to neurodegeneration and cancer, yet post-transcriptional regulation of key repair enzymes remains poorly understood. This study provides the first experimental evidence of miR-103a as a direct regulator of 8-oxoguanine glycosylase 1 (OGG1), a critical enzyme involved in base excision repair, in human astrocytes exposed to oxidative stress. METHODS AND

resultsHuman astrocytes were treated with sodium dichromate (10 µM-100 mM) to induce oxidative stress. MiR-103a was significantly downregulated (p = 1.13141E-77) among the candidates and was predicted in silico to bind the 3' UTR of the OGG1 mRNA. Reverse-transcription PCR analysis confirmed dose-dependent OGG1 upregulation, which was consistent with decreased miR-103a levels. Direct binding was validated through miR-TRAP co-immunoprecipitation, showing a 4-fold enrichment of OGG1 mRNA in miR-103a complexes (p < 0.001). Functional validation using miR-103a inhibitor transfection resulted in significant OGG1 upregulation (p < 0.01), corroborating their reciprocal regulatory relationship.

conclusionsThe miR-103a-OGG1 axis presents a new mechanism for maintaining DNA repair capacity in response to cellular stress. This study provides the first experimental validation of miR-103a as a direct OGG1 regulator, identifying a novel therapeutic target for oxidative stress-related neurological disorders.