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

Gliobastoma continues being an incurable neoplasia, from well established therapeutical protocols, which do not offer much increasing on patients overliving. The hypoxia mechanism associated to cancer stem cells (CSCs), emphasizing the HIF-1α or HIF-2α expression regulation, is directly related to bad prognosis in many types of tumors. Recent studies also prove the microRNAs regulation in molecular targets directly involved with tumoral malignancy, such as HIF-1α, for example. Objective: Our goal was to analyze microRNAs miR-21 and miR-326 expression in the neurospheres of patients diagnosed with gliobastoma and treated with ionizing radiation. These microRNAs were selected for presenting proved relation to the CSCs and HIF-1α regulation. Methods: In this paper, cellular culture of ten patients with gliobastoma was used from surgery biopsies. The cellular viability was evaluated through Trypan Blue after 48 hours of ionizing radiation exposure, then, the aforementioned microRNAs expressions were analyzed through real time PCR. MiR-21 and miR-326 expressions were correlated to death and recurrence by means of the sample group, in general and per group. The ROC curve identified the cut point of the respective microRNAs in relation to the clinical prognosis, separating them by group. Results: By analyzing cellular viability, significant statistical differences were not identified among the neurospheres in experimental groups. Meanwhile, miR-21 presented itself as hyper expressed in the neurospheres group submitted to ionizing radiation treatment (p=0,0028), when compared to the control group, however, it could not be associated to recurrence and death. MiR-326 presented itself associated to tumoral recurrence (p=0,032) in both groups, in which every 0.5 units of miR-326 the chances of recurrence increase 1,024 (2,4%). Conclusions:MiR-21 presented itself hyper expressed in neurospheres group submitted to ionizing radiation treatment suggesting that its role on HIF-1α regulation is related to radioresistant neurospheres. MiR-326 presented itself associated to the increasing chances of recurrence in both groups, neurospheres that were and were not treated though ionizing radiation, also demonstrating that this positive regulation does not depend on the ionizing radiation treatment. (author)