Radiotherapy-associated changes in the miR-۱۲۴/SP۱ axis in a rat glioma model

Objective(s): Glioma is an aggressive brain tumor that frequently involves microRNA dysregulation. Rno-miR-۱۲۴-۳p is a brain-enriched miRNA involved in gene regulation, with Specificity Protein ۱ (SP۱) as its validated target. Radiotherapy remains a cornerstone of glioma treatment; however, its molecular effects on miRNA-transcription factor axes are not fully understood. We hypothesized that radiotherapy up-regulates Rno-miR-۱۲۴-۳p, thereby down-regulating SP۱. Accordingly, this study evaluated their expression following radiotherapy in a rat glioma model.Materials and Methods: C۶ glioma cells were cultured, and an effective radiation dose was determined using an MTT assay. Sixty male Wistar rats were randomly assigned to six experimental groups: control, sham, glioma, and their corresponding radiotherapy-treated groups. Glioma was induced by stereotactic injection of C۶ cells into the striatum. After radiotherapy, brain tissue was collected for histological and molecular analyses. Tumor expression of Rno-miR-۱۲۴-۳p and SP۱ was quantified by real-time PCR. Results: In glioma-bearing rats, Rno-miR-۱۲۴-۳p expression was significantly down-regulated, whereas SP۱ was significantly up-regulated compared with control groups (P≤۰.۰۵ and P≤۰.۰۱, respectively). After radiotherapy, an inverse pattern was observed, with increased Rno-miR-۱۲۴-۳p and decreased SP۱ in glioma tissues (P≤۰.۰۵ and P≤۰.۰۱). Histological evaluation suggested structural differences between the glioma and radiotherapy-treated glioma groups.Conclusion: Glioma development alters the Rno-miR-۱۲۴-۳p/SP۱ regulatory axis. Radiotherapy modulates this molecular pattern, suggesting a potential role for Rno-miR-۱۲۴-۳p in glioma-related pathways. Further studies are needed to clarify its functional and clinical relevance.

کلیدواژه ها:

Animal models ، Gene expression regulation ، Glioma ، microRNAs ، Radiotherapy ، Rno-miR-۱۲۴-۳p ، Sp۱ transcription factor ، Tumor cell line