Abstract
Background
Deficient 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 results
Human 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.
Conclusions
The 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.