Expression of microRNAs miR-21 and miR-326 associated with HIF-1α regulation in neurospheres of glioblastoma submitted to ionizing radiation treatment

Background: Glioblastoma is an incurable neoplasm. Its hypoxia mechanism associated with cancer stem cells (CSCs) demon-strates hypoxia-inducible factor 1 alpha (HIF-1 alpha) expression regulation, which is directly related to tumor malignancy. The aim of this study was to identify a possible tumor malignancy signature associated with regulation of HIF-1 alpha by microRNAs miR-21 and miR-326 in the subpopulation of tumor stem cells which were irradiated by ion in primary culture of patients diagnosed with glioblastoma. Materials and methods: We used cellular cultures from surgery biopsies of ten patients with glioblastoma. MicroRNA expres-sions were analyzed through real-time polymerase chain reaction (PCR) and correlated with mortality and recurrence. The ROC curve displayed the cutoff point of the respective microRNAs in relation to the clinical prognosis, separating them by group. Results:The miR-21 addressed high level of expression in the irradiated neurosphere group (p = 0.0028). However, miR-21 was not associated with recurrence and mortality. miR-326 can be associated with tumoral recurrence (p = 0.032) in both groups; every 0.5 units of miR-326 increased the chances of recurrence by 1,024 (2.4%). Conclusion:The high expression of miR-21 in the irradiated group suggests its role in the regulation of HIF-1 alpha and in the radioresistant neurospheres. miR-326 increased the chances of recurrence in both groups, also demonstrating that positive regulation from miR-326 does not depend on ionizing radiation treatment.

Automated summary

This study aimed to identify a tumor malignancy signature associated with the regulation of HIF-1 alpha by microRNAs miR-21 and miR-326 in glioblastoma stem cells. The results showed that miR-21 had a high level of expression in the irradiated neurosphere group, suggesting its role in radioresistant neurospheres. miR-326 was associated with tumor recurrence in both groups, indicating that its positive regulation is independent of ionizing radiation treatment.